Premature ejaculation is a common symptom that can provoke relapse in formerly opioid-dependent men after detoxification. The purpose of this study was to compare the efficacy of clomipramine and fluoxetine for the treatment of premature ejaculation in formerly opioid-dependent men after detoxification. Sixty opium-detoxified men with A & B DSM-IV diagnostic criteria for premature ejaculation participated in a prospective two-week descriptive inferential clinical trial after a two-week washout period. The subjects did not consume any other medications but naltrexone for maintenance of an opium-free state. The subjects were randomly divided into two groups of thirty subjects, one group received fluoxetine (10 mg/d for the first and 20 mg/d for the second week), and the other received clomipramine (25 mg/d for the first and 50 mg/d for the second week). Twenty five subjects did not continue the treatment and were lost to follow-up. The severity of the premature ejaculation was graded regarding the subjects' report in weeks 0, 1, and 2. Mann Whitney-U and Wilcoxon non-parametric tests were used for statistical analysis. Fluoxetine (10 mg/d then 20 mg/d) and clomipramine (25 mg/d then 50 mg/d) were both effective in the treatment of premature ejaculation and did not show any difference in efficacy. The severity of premature ejaculation did not show any relation to the subjects' age, education level, opioid type, or route of abuse. Fluoxetine and clomipramine both can be equally used in the treatment of premature ejaculation following opioid detoxification, depending on their side effects and other symptoms in the subjects.