Our aim was to investigate the association of corporeal cavernosal pathology with venoocclusive erectile dysfunction (ED) and whether preoperative corporeal biopsy can help predict postoperative results. A total of 36 patients with venoocclusive ED underwent corporeal cavernosal biopsy and venous ligation. Preoperative assessment included complete physical examination, international index of erectile dysfunction (IIEF) scoring, nocturnal penile tumescence, penile Doppler ultrasonography, cavernosography, and, if needed, cavernosometry. Three months after surgery, all patient parameters were reevaluated and compared with the preoperative results. Biopsy results of 43 patients with penile fracture were used for controls. The mean follow-up was 49.0 +/- 24.1 months. The mean age of the patients with ED was 32.1 +/- 8.6 years. Venous leakage was clearly revealed by cavernosography in all patients, preoperatively. The IIEF score and peak systolic velocity of the cavernosal artery in the patients did not differ postoperatively. The mean end diastolic velocity (EDV), however, decreased from 11.0 cm/s to 5.1 cm/s (P = .023). Only 2 patients had satisfactory penile rigidity after venous ligation, 2 were helped by intracorporeal injection to achieve full rigidity, and 1 used oral sildenafil to achieve full rigidity. Pathologically, 23 patients had a slight decrease of cavernosal smooth muscle cells, while in 9 patients, the cavernosal smooth muscles were markedly decreased and replaced by collagen fibers. Four patients had normal histologies, and all responded either partially or completely to surgical therapy. In the control group, 41 of 43 patients had a normal histologies, and 2 had a slight decrease of smooth muscle cell mass. Decreased cavernosal smooth muscle mass may impair erectile function. Its association with venoocclusive ED may be a poor prognostic factor of the outcome of surgical therapy. For the preoperative evaluation of patients, we propose cavernosal biopsy.