Objective: Evidence suggests that the nature and magnitude of some genetic effects on alcohol use vary by age. We tested for moderation in the effect of an alcohol metabolizing polygenic score by time across the college years. Method: Participants (total n = 2,214) were drawn from three cohorts of undergraduate college students, who were assessed annually for up to 4 years starting in their freshman year. Polygenic risk scores (PRSs) were calculated from genes involved in the metabolism of alcohol, as many of these markers are among the best replicated in association studies examining alcohol use phenotypes. Linear mixed effects models were fit by maximum likelihood to test the main effects of time and the PRS on alcohol consumption, as well as moderation of the PRS effect on alcohol consumption by time. Results: In the main effects model, the fixed effects for time and the PRS were positively associated with alcohol consumption. The interaction term testing moderation of the PRS effect by time reached statistical significance and remained statistically significant after other relevant interaction effects were controlled for. The main effect of the PRS accounted for 0.2% of the variance in alcohol consumption, whereas the interaction of PRS effect and time accounted for 0.05%. Conclusions: Alcohol metabolizing genetic effects on alcohol use appear to be more influential in later years of college than in earlier years. Shifting environmental contexts, such as increased access to alcohol as individuals approach the legal age to purchase alcohol, may account for this association.