The Effectiveness of ED Medications and Their Side Effects
Clinical success rates, how PDE5 inhibitors work, side effects compared, and when oral medication may not work.
Part of the Access Doctor Erectile Dysfunction guide.
Key fact: All four MHRA-approved PDE5 inhibitors — sildenafil, tadalafil, vardenafil and avanafil — have comparable clinical efficacy, with success rates of 77–82%. NICE recommends them as equivalent first-line treatment options. The choice between them is based on lifestyle preference, not potency.
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success rate for sildenafil in clinical trials
~81%
success rate for tadalafil in clinical trials
4
MHRA-approved PDE5 inhibitors recommended equally by NICE
How ED Medications Work
All four MHRA-approved ED medications are phosphodiesterase type 5 (PDE5) inhibitors. They work through the same mechanism:
- During sexual stimulation, nerves in the penis release nitric oxide
- Nitric oxide triggers the production of cyclic GMP (cGMP) in the smooth muscle cells lining penile blood vessels
- cGMP causes smooth muscle to relax, widening penile arteries and allowing blood to flow in, producing an erection
- The PDE5 enzyme normally breaks down cGMP, terminating the erection. PDE5 inhibitors block this breakdown, allowing cGMP to accumulate and the erection to be sustained
Sexual stimulation is always required. PDE5 inhibitors do not cause automatic erections — they enhance the natural erectile response when sexual arousal is present.
Effectiveness of Each Medication
| Medication | Active ingredient | Success rate | Onset | Duration | Food effect |
|---|---|---|---|---|---|
| Sildenafil (Viagra) | Sildenafil | ~82% | 30–60 min | 4–6 hours | Yes — avoid fatty meals |
| Tadalafil (Cialis) | Tadalafil | ~81% | ~30 min | Up to 36 hours | No |
| Vardenafil (Levitra) | Vardenafil | ~80% | 25–60 min | 4–6 hours | Mild — avoid fatty meals |
| Avanafil (Spedra) | Avanafil | ~77% | 15–30 min | Up to 6 hours | Minimal |
Success rates in clinical trials are broadly equivalent. For a detailed comparison of all four, see Viagra vs Cialis vs Levitra vs Spedra. To compare the two most commonly prescribed options, see tadalafil vs sildenafil.
Side Effects Compared
All four share a common core of PDE5 inhibitor side effects. The differences are in frequency and pattern:
| Side effect | Sildenafil | Tadalafil | Vardenafil | Avanafil |
|---|---|---|---|---|
| Headache | Very common | Common | Common | Common |
| Flushing | Very common | Common | Common | Less common |
| Nasal congestion | Common | Less common | Common | Common |
| Indigestion | Common | Common | Common | Less common |
| Visual disturbances | More common (blue tinge) | Less common | Uncommon | Rare |
| Back pain / myalgia | Uncommon | More common (long duration) | Uncommon | Uncommon |
| QT prolongation risk | Rare | Rare | Notable — avoid in long QT syndrome | Rare |
All four medications share an absolute contraindication with nitrate medicines (GTN spray, isosorbide mononitrate, recreational “poppers”). The combination causes a severe and potentially fatal blood pressure drop. This is why a prescriber assessment before taking any ED medication is essential. Seek immediate emergency care for priapism (erection >4 hours), sudden vision or hearing loss, or chest pain.
When Oral ED Medication May Have Reduced Effectiveness
PDE5 inhibitors work most effectively when the nitric oxide–cGMP pathway is intact. Their effectiveness is reduced when:
- Taken incorrectly — sildenafil taken after a large fatty meal, or insufficient time allowed before sexual activity
- Diabetic neuropathy and vasculopathy — impaired nitric oxide production reduces response; success rates are 59–67% in diabetic men vs ~82% generally
- Severe cavernous nerve damage (e.g., after non-nerve-sparing prostatectomy) — the nerve-dependent pathway for cGMP release is impaired
- Severe arterial insufficiency — insufficient blood flow regardless of smooth muscle relaxation
- Untreated underlying conditions — poorly controlled diabetes, severe depression, or undiagnosed hypogonadism
In these cases, alprostadil injection therapy (which directly causes vasodilation, bypassing the nitric oxide pathway) or vacuum erection devices remain effective options. For a full overview of when treatment may not work, see is ED treatment guaranteed?
Frequently Asked Questions
How effective are ED medications?
All four MHRA-approved PDE5 inhibitors have high clinical efficacy: sildenafil ~82%, tadalafil ~81%, vardenafil ~80%, avanafil ~77%. Success rates are somewhat lower in men with diabetic neuropathy or severe vascular disease.
What is the most effective ED medication?
All four have comparable efficacy. The choice is based on lifestyle factors — duration of action, food interactions, on-demand vs daily dosing — not potency. NICE recommends all four as equivalent first-line options.
How do ED medications work?
PDE5 inhibitors block the enzyme that breaks down cGMP in penile blood vessels. This allows smooth muscle to relax more easily when sexually stimulated, increasing blood flow into the erectile tissue. Sexual stimulation is always required.
What are the most common side effects of ED medications?
Headache, flushing, nasal congestion, indigestion and dizziness are common to all four. Sildenafil is more associated with visual disturbances; tadalafil with back pain and muscle aches; vardenafil has a notable QT prolongation risk.
When might ED medication not work?
When taken incorrectly, or in men with severe diabetic vasculopathy, cavernous nerve damage (post-prostatectomy), severe arterial insufficiency, or untreated underlying conditions. Alternative options such as alprostadil injection therapy remain available.
References
- National Institute for Health and Care Excellence (NICE). Erectile dysfunction: Clinical Knowledge Summary. Updated 2023. cks.nice.org.uk/topics/erectile-dysfunction
- NHS. Erectile dysfunction (impotence). nhs.uk/conditions/erection-problems-erectile-dysfunction
- Hatzimouratidis K et al. EAU guidelines on erectile dysfunction. Eur Urol. 2010;57(5):804–814. PubMed: 20388436
Medical disclaimer: This article is for informational purposes only and does not constitute medical advice. ED treatments are prescription-only medicines requiring clinical assessment. In a medical emergency, call 999.