OBJECTIVE: In the present study, two different serotonin re-uptake inhibitors were compared with regard to their efficacy and side effects in the treatment of premature ejaculation. METHODS: Fifty-seven patients with complaint of premature ejaculation were included in the study. Patient ages ranged from 21 to 45 years (mean age 32 +/- 2.6). They had a regular sexual life and were normal after GRISS psychological test and psychiatric evaluation. The patients were randomized into two groups according to the drugs given. Twenty-six patients aged between 21 to 36 years (mean age 27 +/- 1.1) received fluoxetine 20 mg/day for one week and 40 mg/day thereafter (group I). Thirty-one patients aged between 21 to 45 (mean age 34 +/- 1.7) received sertraline 50 mg/day (group II). All the patients and partners were re-evaluated 4 and 8 weeks after the treatment. The results were classified as unsuccessful, improvement and cure. Mann Whitney-U and Pearson chi-square tests were used for statistical analysis. RESULTS: In the fluoxetine group, 8 (30.8%) patients cured, improvement in 11 (42.3%) and failure in 7 (26.9%). In the sertraline group, 12 (38.7%) patients cured, improvement in 10 (32.3%) and failure in 9 (29%). Side effects in group I were nausea in 3, headache in 1 and insomnia in 2 (total 6 patients, 23%). In group II, we observed nausea in 2 and mouth dryness in 6 (total 8 patients, 25.8%). No patients were excluded from the study due to side effects. CONCLUSION: Our results show that different serotonin re-uptake inhibitors have the same efficacy and side effects in the treatment of premature ejaculation.