ED medication timing: what clinical trials show

The difference between ED medication working well and not working at all often comes down to timing. And the gap between treatments is bigger than most men realise.

Clinical trials using stopwatches at home have produced precise data on how quickly each medicine can start working. This article breaks down what those studies actually found, and how it fits with the instructions on your pack.

You still need to feel aroused for any ED tablet to work. They help your body respond, they don't create an erection on their own.

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Why timing matters

All four ED treatments available at Pharmica, sildenafil, tadalafil, vardenafil and avanafil, block an enzyme called PDE5. That increases blood flow to the penis when you're sexually stimulated. None of them works without sexual stimulation.^1,2,3,4

If an ED tablet doesn't seem to work, timing is one of the first things worth checking. Each medicine has its own recommended window, and taking it too late, or straight after a big meal, can make it seem as though it's failed.^1,4

Understanding what the trials found for each treatment gives you a clearer picture of how each one behaves. That gives you a better chance of getting it right.

For other slip-ups that can get in the way, see our guide to common ED medication mistakes.

One safety rule applies to all four. ED tablets must not be taken with nitrates for chest pain, or with poppers (amyl nitrite), because the combination can cause a dangerous drop in blood pressure.^1,4

Never mix an ED tablet with nitrate heart medicines or poppers. Getting the timing right does not make this combination safe.

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What "onset" means in the clinical trials

Before going through each treatment, it helps to know how "onset" is measured in these trials.

The gold standard is time to successful intercourse. Men used a stopwatch from the moment they took the dose until they had an erection firm enough for penetration that led to completed sex.⁵ It's a real-world measure of what matters, not a lab measure of how much medicine is in the blood.

Some clinic studies use devices called RigiScan monitors to pick up early changes in erection firmness instead. This article sticks to the at-home stopwatch trials, which are the most useful in practice.

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Sildenafil: what the stopwatch studies found

Sildenafil's product information says to take it about an hour before sex.¹ A landmark trial designed to measure the fastest time it starts working added useful detail.

The trial involved 228 men who already knew sildenafil worked for them (115 on sildenafil 100mg, 113 on placebo). They took their dose at least 2 hours after eating, and used a stopwatch from dose to an erection good enough for successful sex.⁵

At 14 minutes, 35% of men on sildenafil had an erection that led to successful sex, compared with 22% on placebo. By 20 minutes, it was 51% compared with 30%. The middle (median) time to an erection that led to successful sex was 36 minutes.⁵

That's faster than the pack suggests. The one-hour instruction lines up with when blood levels usually peak, which is anywhere from 30 to 120 minutes after a dose, typically 60.¹ But the trial showed the medicine can start working before that peak.

The men in this trial were already sildenafil users, so treat those quick times as a best case. The one-hour guide on your pack is still the place to start.

In practice, follow the timing on your label. Sildenafil may take longer to start working if you take it with food.¹

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Tadalafil: earlier onset than most men expect

Tadalafil stays in your body far longer than any other licensed PDE5 inhibitor. Its half-life is around 17.5 hours.² That's what's behind its 36-hour window and the daily 5mg option.

Its blood levels peak at around 2 hours, much later than sildenafil.² That leads many men to assume it's slow to start working. A dedicated at-home trial tested that assumption.

In the trial, men with ED tried to have sex within 30 minutes of taking tadalafil 10mg, 20mg or placebo, on four separate occasions, timing it with a stopwatch.⁶

The key finding: tadalafil 20mg was working measurably better than placebo from 16 minutes after the dose. 52% of men on tadalafil 20mg had at least one successful attempt within 30 minutes, compared with 35% on placebo.⁶

Tadalafil's long window takes the pressure off. If the first hour doesn't go to plan, it can still work for many hours afterwards.

So tadalafil can start working noticeably earlier than its peak blood level would suggest.

In practice, on-demand tadalafil (10mg or 20mg) can be taken at least 30 minutes before sex. And it can keep working for up to 36 hours after a dose.²

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Vardenafil (Levitra): the fastest first-generation option

Vardenafil, also sold as Levitra, is usually taken 25 to 60 minutes before sex. Its blood levels peak at a similar time to sildenafil, typically around 60 minutes, although in some men it peaks as early as 15 minutes.³

A large at-home trial involved 732 men: 237 on vardenafil 10mg, 248 on vardenafil 20mg and 247 on placebo. They recorded the time from dose to an erection firm enough for penetration with a stopwatch, over their first four doses.⁷

In men who responded, vardenafil worked better than placebo from as early as 10 to 11 minutes after the dose.⁷ Looking back at the data, 75 to 77% of attempts made within 15 to 30 minutes of dosing were successful in men taking vardenafil, compared with 45 to 47% on placebo.⁷

Across the three first-generation medicines, the earliest point at which each trial picked up an effect was 14 minutes for sildenafil, 16 minutes for tadalafil 20mg and 10 to 11 minutes for vardenafil.^5,6,7

These come from separate trials with different designs, so they aren't a direct comparison. The differences at the earliest time points are small. For most men, the more useful difference between vardenafil and sildenafil isn't how fast they work, but how food affects them.

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Avanafil (Spedra): the timing case for a second-generation drug

Spedra (avanafil) has the shortest recommended lead time of the four. You take it around 15 to 30 minutes before sex, and its blood levels peak at around 30 to 45 minutes.⁴

A randomised trial of 440 men with ED looked at successful sex within around 15 minutes of taking avanafil 100mg, 200mg or placebo, over 8 weeks, using a stopwatch.⁸

Both doses of avanafil led to significantly more successful attempts within 15 minutes than placebo. The difference was significant from 10 minutes after the dose with 200mg, and from 12 minutes with 100mg.⁸

A separate head-to-head trial of 220 men compared avanafil with sildenafil. It found avanafil had a faster onset of action.⁹ That's one trial, so it's a useful pointer rather than the final word.

So avanafil is the option to consider if the longer planning window of the first-generation medicines really doesn't work for you. Like sildenafil, it may take longer to work if you take it with food.⁴

Spedra is the one built around short notice. Around 15 to 30 minutes is the usual lead time, ideally without a big meal first.

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How food changes the timing equation

Food is where the timing differences between treatments matter most in practice. For more on sildenafil, see our guide to taking Viagra with food.

Sildenafil is clearly affected by food. Taken with food, its peak blood level comes around an hour later, and is around 29% lower.^1,10 The product information says this may delay when it starts working.¹

Real-world results can be more forgiving. In one trial of men already happy with sildenafil, taking it an hour before or during a normal meal made no significant difference to how well it worked.¹¹ So a light meal is unlikely to stop it working. But if it seems slow after a big, heavy meal, food is the first thing to look at.

Vardenafil is affected in a similar way, but only by high-fat meals. A high-fat meal can delay its peak by about an hour, while a moderate-fat meal makes no real difference.^3,12 So take it on an empty stomach or after a lighter meal.

Tadalafil isn't affected by food. You can take it with or without a meal.² That's a practical advantage if timing around meals is difficult for you.

Planning a dinner date? Tadalafil isn't affected by food, so it's the easiest to time around a meal.

Avanafil can be taken with or without food, but a high-fat meal may delay when it starts working.⁴

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What this means for choosing a treatment

The trial data on timing points to a few practical conclusions.

GPhC Number 2088658

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Avanafil has the shortest licensed lead time, at around 15 to 30 minutes before sex. Tadalafil can be taken at least 30 minutes before sex and can keep working for up to 36 hours. Whichever you use, follow the timing and dose on your own medicine's label, and do not take it with nitrates or poppers.

If spontaneity and minimal planning matter most, avanafil (Spedra) has the shortest licensed lead time and trial evidence for working within around 15 minutes.^4,8

If you can plan ahead and how long it lasts matters more, tadalafil gives you a window of up to 36 hours, and can be taken at least 30 minutes before sex. The daily 5mg version takes timing decisions out of the picture entirely.²

If you want a well-studied option with early onset, sildenafil is a good fit. But keeping big meals away from your dose may help it work faster.¹

Vardenafil (Levitra) sits in similar territory to sildenafil on timing.

Whichever you use, follow the timing and dose on your own medicine's label. Get urgent medical help if you have chest pain during or after sex, or an erection that lasts more than 4 hours.^1,13

Chest pain, or a painful erection that will not go down, is an emergency. It is not a side effect to wait out.

Not sure which suits you? The ED Trial Pack lets you compare two or more treatments, such as sildenafil and tadalafil, before committing to one.

If you do try more than one, never take two different ED tablets together. Ask your prescriber how long to leave between them, because tadalafil stays in your body well beyond the day you take it.²

The full range of ED treatments available at Pharmica includes all four active ingredients discussed in this article.

If you get ED treatment through Pharmica, we'll ask you to see your GP for a clinical review within 6 months of starting. The consultation also asks about previous ED medicine use and your health, and a prescriber decides which treatment and schedule suit you.

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References

1. Viatris Products Limited. Viagra 50 mg film-coated tablets: Summary of Product Characteristics. Electronic Medicines Compendium; 2025. medicines.org.uk/emc
2. Eli Lilly Nederland B.V. Cialis 20mg film-coated tablets: Summary of Product Characteristics. Electronic Medicines Compendium; 2026. medicines.org.uk/emc
3. Generics [UK] Limited t/a Mylan. Vardenafil Mylan 20 mg film-coated tablets: Summary of Product Characteristics. Electronic Medicines Compendium; 2025. medicines.org.uk/emc
4. Menarini International Operations Luxembourg S.A. Spedra 100 mg tablets: Summary of Product Characteristics. Electronic Medicines Compendium; 2024. medicines.org.uk/emc
5. Padma-Nathan H, Stecher VJ, Sweeney M, et al. Minimal time to successful intercourse after sildenafil citrate: results of a randomized, double-blind, placebo-controlled trial. Urology. 2003;62(3):400-403. doi:10.1016/s0090-4295(03)00567-3
6. Rosen RC, Padma-Nathan H, Shabsigh R, et al. Determining the earliest time within 30 minutes to erectogenic effect after tadalafil 10 and 20 mg: a multicenter, randomized, double-blind, placebo-controlled, at-home study. The Journal of Sexual Medicine. 2004;1(2):193-200. doi:10.1111/j.1743-6109.2004.04028.x
7. Montorsi F, Padma-Nathan H, Buvat J, et al. Earliest time to onset of action leading to successful intercourse with vardenafil determined in an at-home setting: a randomized, double-blind, placebo-controlled trial. The Journal of Sexual Medicine. 2004;1(2):168-178. doi:10.1111/j.1743-6109.2004.04025.x
8. Hellstrom WJ, Kaminetsky J, Belkoff LH, et al. Efficacy of Avanafil 15 Minutes after Dosing in Men with Erectile Dysfunction: A Randomized, Double-Blind, Placebo Controlled Study. Journal of Urology. 2015;194(2):485-492. doi:10.1016/j.juro.2014.12.101
9. Kumar M, Pathade AD, Gupta SV, et al. Efficacy and safety of avanafil as compared with sildenafil in the treatment of erectile dysfunction: A randomized, double blind, multicenter clinical trial. International Journal of Urology. 2022;29(4):351-359. doi:10.1111/iju.14785
10. Nichols DJ, Muirhead GJ, Harness JA. Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. British Journal of Clinical Pharmacology. 2002;53(Suppl 1):5S-12S. doi:10.1046/j.0306-5251.2001.00027.x
11. Zinner N. Do food and dose timing affect the efficacy of sildenafil? A randomized placebo-controlled study. The Journal of Sexual Medicine. 2007;4(1):137-144. doi:10.1111/j.1743-6109.2006.00400.x
12. Rajagopalan P, Mazzu A, Xia C, et al. Effect of high-fat breakfast and moderate-fat evening meal on the pharmacokinetics of vardenafil, an oral phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction. The Journal of Clinical Pharmacology. 2003;43(3):260-267. doi:10.1177/0091270002250604
13. NHS. Sildenafil: a medicine for erection problems. NHS website; 2026. nhs.uk

This article is intended for informational purposes only and does not replace professional medical advice. Always read the patient information leaflet supplied with your medication and speak to a healthcare professional if you have specific concerns.