The association between posttraumatic stress disorder (PTSD) and harmful alcohol use has often been explained through the self-medication hypothesis via coping-related drinking motives. However, the magnitude of the indirect effect of PTSD on harmful alcohol use through coping motives is unclear. This study aggregated this indirect effect using a meta-analytic structural equation modeling approach and explored moderators that influenced the indirect effect. We identified articles from PsycINFO, PubMed/MEDLINE, and PROQUEST (through June 22, 2021) containing measures of (a) PTSD symptoms, (b) coping-related drinking, and (c) harmful alcohol use. Thirty-four studies yielding 69 effect sizes were included (mean N = 387.26 participants; median N = 303.5; range = 42-1,896; aggregate sample n = 15,128). Coping motives mediated the relation between PTSD and harmful alcohol use, accounting for 80% of the variance in the total effect. Moderating variables and evidence of publication bias were also found. Findings suggest that coping-related drinking is a strong mediator in the relation between PTSD and harmful alcohol use and that the strength of the indirect effect is meaningfully influenced by measurement approach, sample characteristics, and study design. Additional longitudinal and multivariate studies are needed to establish directionality and account for additional variance. (PsycInfo Database Record (c) 2022 APA, all rights reserved).