BACKGROUND AND OBJECTIVES: Posttraumatic stress disorder (PTSD), depression, anxiety, and stress are significant problems among returning veterans and are associated with reduced quality of life. DESIGN: A correlational design was used to examine the impact of a polymorphism (5-HTTLPR) in the serotonin transporter promoter gene on post-deployment adjustment among returning veterans. METHODS: A total of 186 returning Iraq and Afghanistan veterans were genotyped for the 5-HTTLPR polymorphism. Symptoms of PTSD, depression, general stress, and anxiety were assessed along with quality of life. RESULTS: After controlling for combat exposure, age, sex of the participant, and race, 5-HTTLPR had a significant multivariate effect on post-deployment adjustment, such that S' carriers reported more post-deployment adjustment problems and worse quality of life than veterans homozygous for the L' allele. This effect was larger when the analyses were restricted to veterans of European ancestry. CONCLUSIONS: Our findings suggest that veterans who carry the S' allele of the 5-HTTLPR polymorphism may be at increased risk for adjustment problems and reduced quality of life following deployments to war zones.