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Drinking in unfamiliar social settings has long been linked to alcohol problems. A large body of indirect evidence has accumulated to suggest that alcohol’s rewarding subjective effects—both tension relieving and positive-mood enhancing—will be magnified when it is consumed among strangers versus among familiar individuals. But the link between social familiarity and alcohol reward has never been examined. I conducted a meta-analysis of 21 alcohol-administration studies featuring social context (total N = 2,046), examining the effects of alcohol on self-reports of mood and social outcomes and on behaviors in the context of social interactions. Studies were classified according to whether participants involved in the social interaction were previously acquainted prior to study participation (familiarity condition) and also according to other characteristics of the social interaction and alcohol-dosing procedure. Results of random effects metaregression models revealed a significant effect of familiarity in moderating alcohol response, Q(1) = 9.80, p = .0002. Alcohol-related social–emotional enhancement was significantly larger when studies examined interactions among strangers (d = .48, 95% confidence interval [CI: .34, .61]) versus when they examined interactions among familiar individuals (d = .09, 95% CI [−.12, .29]). Of note, in analyses examining self-reports and behaviors separately, findings indicated that alcohol consumption leads to similar behavioral disinhibition across familiar and unfamiliar contexts but that the consequences of this disinhibition for internal subjective experience may differ depending on familiarity. Overall, results suggest that individuals may gain more subjective reward from alcohol in unfamiliar social contexts, pointing to familiarity as a potentially promising line of inquiry for research examining mechanisms of risk for alcohol problems.