Abstract: Objectives: Posttraumatic stress disorder (PTSD) may affect antiretroviral therapy (ART) response and clinical outcomes for veterans with HIV (VWH) receiving care in the Department of Veterans Affairs (VA). Objectives: are to estimate the associations between PTSD and ART nonadherence, modifications, and failure; measure effect modification by number of deployments and combat exposure; and examine how these associations vary over time. Design: In this prospective cohort study of all VWH on ART who deployed to Iraq and Afghanistan and receive care in the VA ( n = 3206), patients entered at ART initiation and were censored in December 2022, totaling 22 261 person-years of follow-up. Methods: Marginal structural log-binomial and Poisson models were fitted with a time-dependent exposure, adjusted for time-independent and time-dependent confounding and informative censoring, to estimate the associations between PTSD and ART nonadherence, modifications, and failure. Marginal structural shared frailty models were fitted to examine time-varying associations. Results: PTSD increased the risk [adjusted risk ratio, 95% confidence interval (CI)] of ART nonadherence by 6% (1.06 [1.00, 1.13]) and the rate (adjusted incidence rate ratio, 95% CI) of ART modifications by 38% (1.38 [1.19, 1.58]). Multiple deployments amplified the association with ART nonadherence by 14%; combat exposure did not modify any association examined. The association with ART modifications increased during the first decade post-PTSD-diagnosis but subsequently stabilized. Conclusions: PTSD increased ART nonadherence and ART modifications. Providers should screen for PTSD so that it can help guide medical decisions and treatment; particular attention should be paid to Veterans with multiple combat deployments.