To compare the efficacy and safety of available selective serotonin reuptake inhibi-tors (SSRIs) in order to find the most effective drug with the least number of side effects in treatment of premature ejaculation (PE).This study was a randomized clinical trial. Four hundred and eighty pati-ents with PE in the 4 groups referred to Imam Reza hospital Tehran, Iran from July 2018 to Fe-bruary 2019 were enrolled in the study. The patients received sertraline 50mg, fluoxetine 20mg, paroxetine 20mg and citalopram 20mg, every 12 hours daily. The intravaginal ejaculatory laten-cy time (IELT) before treatment, fourth and eighth weeks after treatment was recorded by the patient's wife with a stopwatch.Mean IELT before, 4 and 8 weeks after treatment in four groups were: sertraline 69.4±54.3, 353.5±190.4, 376.3±143.5; fluoxetine 75.5±64.3, 255.4±168.2, 314.8±190.4; paroxeti-ne 71.5±69.1, 320.7±198.3, 379.9±154.3; citalopram 90.39±79.3, 279.9±192.1, 282.5±171.1 seconds, respectively. The ejaculation time significantly increased in all groups (p <0.05), but there was no significant difference between the groups (P=0.75). Also, there was no significant difference in drugs side effects between groups (p >0.05). The most common side effects were drowsiness and dyspepsia, which were not severe enough to cause discontinuation of the drug.All available SSRIs were effective and usually had no serious complications. In patients who did not respond to any of these drugs, other SSRI drugs could be used as a salvage therapy.