Background: Heavy and/or harmful alcohol use while in college is a perennial and significant public health issue. Despite the plethora of cross-sectional research suggesting deleterious effects of alcohol on the brain, there is a lack of literature investigating the longitudinal effects of alcohol consumption on the adolescent brain. We aim to probe the longitudinal effects of college drinking on gray matter change in students during this crucial neurodevelopmental period.Methods: Data were derived from the longitudinal Brain and Alcohol Research in College Students (BARCS) study of whom a subset underwent brain MRI scans at two time points 24 months apart. Students were young adults with a mean age at baseline of about 18.5 years. Based on drinking metrics assessed at both baseline and followup, subjects were classified as sustained abstainers/light drinkers (N = 45) or sustained heavy drinkers (N = 84) based on criteria established in prior literature. Gray matter volumetric change (GMV-c) maps were derived using the longitudinal DARTEL pipeline as implemented in SPM12. GMV-c maps were then subjected to a 1-sample and 2-sample t-test in SPM12 to determine within- and between-group GMV-c differences in drinking groups. Supplementary between-group differences were also computed at baseline only.Results: Within-group analysis revealed significant decline in GMV in both groups across the 2 year followup period. However, tissue loss in the sustained heavy drinking group was more significant, larger per region, and more widespread across regions compared to abstainers/light drinkers. Between-group analysis confirmed the above and showed a greater rate of GMV-c in the heavy drinking group in several brain regions encompassing inferior/medial frontal gyrus, parahippocampus, and anterior cingulate. Supplementary analyses suggest that some of the frontal differences existed at baseline and progressively worsened.Conclusion: Sustained heavy drinking while in college was associated with accelerated GMV decline in brain regions involved with executive functioning, emotional regulation, and memory, which are critical to everyday life functioning. Areas of significant GMV decreases also overlapped largely with brain reward and stress systems implicated in addictive behavior.