Using a large and nationally representative sample, we examined how adolescents’ 5-HTTLPR genotype and perceived parenting quality independently and interactively associated with trajectories of alcohol use from early adolescence to young adulthood and whether/how gender may moderate these associations. The sample for this study included 13,749 adolescents (53.3% female; 56.3% non-Hispanic White, 21.5% Black, 16.0% Hispanic, and 6.1% Asian) followed prospectively from adolescence to young adulthood. Using growth mixture modeling, we identified four distinct trajectories of alcohol use (i.e., persistent heavy alcohol use, developmentally limited alcohol use, late-onset heavy alcohol use, and non/light alcohol use). Results indicated that the short allele of 5-HTTLPR was associated with higher risk of membership in the persistent and the late-onset heavy alcohol use trajectories. Parenting quality was associated with lower likelihoods of following the persistent heavy and the developmentally limited alcohol use trajectories but was not associated with risk of membership for the late-onset heavy drinking trajectory. 5-HTTLPR interacted with parenting quality to predict membership in the persistent heavy alcohol use trajectory for males but not for females. Findings highlighted the importance of considering the heterogeneity in trajectories of alcohol use across development and gender in the study of Gene Environment interactions in alcohol use.