In this study, we aimed at evaluating the efficacy and safety of venlafaxine extended release 75 mg, a serotonin and noradrenaline reuptake inhibitor, in the treatment of patients with premature ejaculation. Thirty-one patients with intravaginal ejaculation latency of less than 2 min received venlafaxine XR (75 mg/day) or placebo during a 2-week period for each agent with a washout period of 1 week between agents. Efficacy was assessed for each agent with changes in ejaculation latency measured with a stopwatch and sexual satisfaction scores of patients and partners. Side-effects, pre- and post-treatment levels of biochemical and spermiogram parameters, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin and total testosterone were recorded for each agent. Statistical analysis was performed on 21 patients. After 2 weeks of treatment with placebo and venlafaxine, ejaculation latency time was significantly increased from 60.1 +/- 39.1 to 126.9 +/- 98.3 sec and to 178.1 +/- 122.8 sec, respectively (p < 0.0001 for each one). However, the difference between the two agents was insignificant (p = 0.144). Venlafaxine and placebo increased sexual satisfaction scores of both patients and partners similarly, no statistically significant difference was found between them in this respect. The incidence of side-effects with venlafaxine was indifferent than that of placebo (p > 0.1) except nausea (p = 0.035). Both agents did not change the blood and spermiogram parameters significantly, except FSH increases. Short-term use of venlafaxine XR 75 mg has only a placebo effect on ejaculation latency and sexual satisfaction scores, therefore, is not appropriate for the patients with premature ejaculation. Further dose-time studies are required to draw final conclusions on the inefficacy of this drug in premature ejaculation.