The discontinuation rate with phosphodiesterase type 5 inhibitors (PDE5i) remains very high. Recently, a new PDE5ì, avanafil, has become available worldwide. Areas covered: All placebo-controlled randomized clinical trials (RCTs) on the effect of avanafil in patients with ED were reviewed and meta-analyzed. So far, 5 different RCTs on avanafil have been published, including 1379 and 605 patients in active and placebo groups, respectively. Avanafil was up to 3-fold superior to placebo in determining successful sexual intercourse. Although head-to-head comparative studies are still lacking, re-analyses of available data, showed that avanafil had comparable efficacy, but lower incidence of drug-related side effects, compared to first-generation PDE5is. Expert opinion: Avanafil specific and peculiar pharmacological profile, addresses several problems that have been documented with first-generation PDE5is. Avanafil should theoretically guarantee a low dropout incidence by ensuring a natural profile of action and a low incidence of side effects. Longer studies and head-to-heard trials are advisable to clarify these issues.