Erectile dysfunction (ED) and depression are highly prevalent and frequently comorbid. Sildenafil effectively treats ED in men with depression and in men taking antidepressants. We evaluated the efficacy of sildenafil in men with depression in remission and ED. Patients with a history of ED when major depressive disorder (MDD) was diagnosed, which persisted after MDD was treated to remission, were randomized to 12 weeks of treatment with sildenafil (50 mg, flexible) or placebo. Efficacy was assessed using intercourse success rates, a global efficacy question (Has treatment improved your erections?), the International Index of Erectile Function (IIEF) and Life Satisfaction Checklist (LSC). By week 12, intercourse success rates were significantly higher among sildenafil- (74%) compared to placebo-treated patients (29%; P=0.0001). About 83% and 34% of sildenafil- and placebo-treated patients, respectively, reported improved erections (odds ratio=9.4, P=0.0001). IIEF scores in the sildenafil group (n=83) were significantly improved compared to those in the placebo group (n=85; P < 0.0001). LSC sexual life item improved significantly among sildenafil- versus placebo-treated patients. The most frequently reported adverse events were transient and mild-to-moderate. Sildenafil is an effective and well-tolerated treatment for ED in patients with a history of ED at the time of MDD diagnosis, and which persisted after the MDD was treated to remission.