The goal of this study was to assess the therapeutic benefits of long-acting testosterone therapy in hypogonadal patients with erectile dysfunction (ED). We recruited 29 patients with ED, ranging in age from 32 to 65 years (mean +/- SD, 47 +/- 9.7 years), with low plasma testosterone, who did not respond to phosphodiesterase type 5 inhibitor therapy. To evaluate penile arterial and venous blood flow, we employed duplex Doppler ultrasonography. For confirmation of diagnosis of venous leakage, pharmacocavernosography was carried out in 9 patients and magnetic resonance imaging with intracavernous contrast enhancement was carried out in 8 patients. All patients were treated with 1000 mg injectable testosterone undecanoate on day 1, followed by another injection after 6 weeks and every 3 months thereafter, in accordance with Nebido therapy protocol. Plasma testosterone levels were determined in all patients at baseline and after 18 and 30 weeks of testosterone treatment. The International Index of Erectile Function (IIEF-5) was administered at baseline and after 18 and 30 weeks of testosterone treatment. At baseline total testosterone ranged from 7 to 11.8 nmol/L (200 to 345 ng/dL) in 25 patients. Eighteen and 30 weeks after testosterone treatment, the mean testosterone plasma levels were 18 and 21.5 nmol/L (520 and 625 ng/dL), respectively. After 18 and 30 weeks of testosterone treatment, 20 out of the 29 patients demonstrated marked improvement in erectile function domain, as assessed by the IIEF-5. This was also associated with diminution of venous leakage. We suggest that, in hypogonadal men with ED, testosterone therapy improves erectile function in patients with ED and venous leakage.