The objective was to compare the efficacy and safety of the as needed use of clomipramine, sertraline, paroxetine, sildenafil and the pause-squeeze technique in treatment of primary premature ejaculation. A prospective double blind randomized crossover study involving 31 patients was performed. Treatment phases comprised five 4-week consecutive treatment periods, each separated by a two-week washout period. Patients were randomly assigned to receive each of the 4 drugs and use pause-squeeze on an as needed basis. Drugs were administered 3 to 5 hours before anticipated coitus. Anxiety score and ejaculation latency time were measured before treatment, after each treatment, and during washout periods. Sexual satisfaction score was measured after each treatment. The median ejaculation latency time was significantly increased from the pretreatment median of 1 minute to 4 minutes, 3 minutes, 4 minutes, 15 minutes and 3 minutes during treatment with clomipramine, sertraline, paroxetine, sildenafil and pause-squeeze technique, respectively (all P 0.0001). Sildenafil was superior to other modalities in terms of ejaculation latency and satisfaction (P = 0.0001). The three antidepressants were comparable to each other in terms of efficacy (P > 0.05). Paroxetine was superior to the pause-squeeze technique in terms of efficacy (P < 0.05). In conclusion, sildenafil appears to be superior to other modalities and a valid alternative in treatment of premature ejaculation. The 3 antidepressants were equivalent to each other in terms of efficacy and safety. Paroxetine was superior to pause-squeeze technique in terms of efficacy.