Background The symptomatology of posttraumatic stress disorder (PTSD) is related not only to the intensity of the causative trauma, but also to alcohol use and genetic factors. Among the many candidate genes, the apolipoprotein E gene (APOE) is thought to be associated with stress reactivity. Methods Korean veterans of the Vietnam War with (n = 128) or without (n = 128) PTSD participated in this study. The Clinician‐Administered PTSD Scale and Combat Exposure Scale were administered, and the severity of alcohol use was assessed among these veterans. The APOE polymorphism and clinical variables of the subjects were compared, and associations between PTSD and potential explanatory variables were tested using logistic regression analysis. Results Higher frequencies of APOE ε2 alleles and a greater number of individuals with the ε2 allele were found in the PTSD group. Among patients with PTSD, ε2‐allele noncarriers consumed alcohol in greater amounts and more frequently than did ε2‐allele carriers. Regression analysis revealed a significant interactional effect between harmful drinking and the absence of the ε2 allele associated with PTSD risk. Conclusions These results suggest that the APOE ε2 allele operates as a susceptibility gene for combat‐related PTSD, with the relationship between alcohol use and PTSD differing according to the ε2‐allele status. Future studies should determine the role of the APOE in adaptation to extreme stress, the development of PTSD, and comorbid alcohol‐related disorders.