A possible synergistic effect between penile venous surgery and oral sildenafil was inadvertently found in treating patients with erectile dysfunction in our clinic. We therefore sought to elucidate the possible synergic effect between venous surgery and sildenafil through studying patients who were non-responders preoperatively. From July 1998 to July 2003, 128 patients were diagnosed with veno-occlusive dysfunction. Subsequently, 65 of them underwent penile venous surgery and were assigned to the surgical treatment group. The remaining 63 men were assigned to the control group, and were subject to a simple re-exposure of oral sildenafil. All patients were evaluated with the international index of erectile function (IIEF-5) scoring. Sildenafil (12.5-100 mg) was prescribed postoperatively to all surgical patients as venous surgery alone was unsatisfactory and similarly, 100 mg preparation was prescribed for patients in the control group. The IIEF-5 scoring in the control group changed from a preoperative mean IIEF-5 score of 9.4 +/- 3.9 to 10.7 +/- 3.5 postoperatively. In surgical patients, however, the mean preoperative IIEF-5 score of 9.2 +/- 5.0, which increased to 15.1 +/- 5.0 (p < 0.001) postoperatively, further increased to 20.1 +/- 5.4 (p < 0.0001) after the addition of sildenafil. Although there was no significant difference between the two groups characteristics, there was a statistically significant difference between treatment results (p < 0.001). Overall, 61 men (93.8%) reported a positive response to sildenafil after venous stripping surgery. In contrast, only eight patients (12.7%) felt a beneficial response in the control group (p < 0.001). Forty-one of 65 patients had scores of > or =22, and 19 of these had a score of 25. No response was found in three (4.6%), and a decrease of 7 was seen in one (1.5%). In summary, patients in whom sildenafil was not effective preoperatively can become excellent responders after careful penile venous surgery. It appears that together, oral sildenafil and penile venous surgery may provide an encouraging solution to impotent patients with veno-occlusive dysfunction who are non-responders to sildenafil.