Selective serotonin reuptake inhibitors (SSRIs) are increasingly used to treat premature ejaculation. We report a large prospective placebo-controlled crossover study of sertraline in premature ejaculation (PE) using Arabic Index of Premature Ejaculation (AIPE). One hundred and forty-seven men suffering from PE were enrolled in a randomized single-blinded crossover study of sertraline hydrochloride and placebo. Patients were randomized into group 1 (n=77) and group 2 (n=70). Both groups received sertraline and placebo interchangeably for 4 weeks. Overall, 127 (81%) of 157 subjects experienced a significant increase in their AIPE total score after sertraline treatment. Sixty-six (66%) of 100 patients available for follow-up experienced relapse of PE within 6 months after sertraline withdrawal. The active drug was generally well tolerated. Our relatively large study, using a validated questionnaire (AIPE), confirmed the useful effect of sertraline on PE.