Given the evidence from retrospective studies indicating that alcohol-dependent patients with homozygous or heterozygous A118G variant of the μ-opioid receptor, OPRM1, gene have significantly better outcomes when treated with naltrexone; this study examined this prospectively in 100 alcohol-dependent participants prescribed naltrexone for 12 weeks and offered six sessions of cognitive-behavioral therapy or intervention. Comparisons were made among OPRM1 genotypic groups on several outcome measures. Naltrexone treatment produced significant decreases in self-reported and objective indicators of alcohol use and craving from baseline (P<0.0001 and 0.017, respectively), particularly during the first 2 months of treatment, with 68% completing the study. However, there was no evidence of a significant association between OPRM1 A118G genotype and treatment success on any of the outcome measures. Therefore, while naltrexone was an effective treatment for alcohol dependence, the OPRM1 A118G genotype was not a predictor of success.