Human laboratory and animal models implicate variation in the μ‐opioid receptor gene (OPRM1) as relevant for alcohol‐related reward. OPRM1 is associated with alcohol self‐administration in non‐human primate studies, but the relevance of this finding to human models is unclear. This study used computer‐assisted self‐infusion of ethanol (CASE) to examine associations among OPRM1 A118G genotype, subjective responses to alcohol and intravenous alcohol self‐administration in young heavy drinkers (n = 40, mean age = 19.95 years, SD = 0.82). Participants completed a 2‐hour CASE session comprising a priming phase followed by ad libitum self‐administration in a free‐access paradigm. Participants achieved a mean peak breath alcohol concentration (BrAC) of 81.18 mg% (SD = 24.96). Those with the OPRM1 118G variant (GA or GG genotypes) achieved significantly higher peak BrAC (M = 94.90 mg%, SD = 16.56) than those with the AA genotype (M = 74.46 mg%, SD = 25.36), reflecting a significantly greater number of alcohol requests among GA/GG participants. Eighty percent of GA/GG participants surpassed a threshold defining a laboratory analog of heavy alcohol exposure (80 mg%) compared with 46 percent of AA participants. Results indicated significant associations between subjective measures of alcohol sensitivity and CASE outcomes, although the pattern of findings differed across self‐report measures. Subjective responses did not differ by OPRM1 status. These results offer further support for the feasibility of the CASE paradigm and provide initial evidence for an association of OPRM1 with alcohol self‐administration in a human laboratory context.