The purpose of this work was to investigate the efficacy and safety of sildenafil in combination with doxazosin for the treatment of non-organic erectile dysfunction in patients who did not respond to sildenafil. We enrolled 28 patients with non-organic erectile dysfunction, for whom 3 months of sildenafil monotherapy had failed. They were divided in two random and homogeneous groups: 14 were treated with doxazosin (4 mg daily) and sildenafil (100 mg 1 h before sexual intercourse); the other 14 patients received sildenafil and placebo. The results were assessed by means of the IIEF questionnaire before the beginning of the study, after 30 days of therapy and after 60 days. Of the 14 patients treated with doxazosin and sildenafil, 11 (78.6%) showed a statistically significant increase of IIEF; in the placebo group, only one patient (7.1%) recorded a significant IIEF increase. The differences observed in the two groups were statistically very significant (P=0.0016). Blood pressure did not show significant alterations. Side effects were minimal and even present during sildenafil monotherapy. The combination therapy with sildenafil and doxazosin resulted in the safe and effective treatment of men with non-organic erectile dysfunction for whom sildenafil alone had failed.