Posttraumatic stress disorder (PTSD) is a significant problem for a large number of veterans who receive treatment from the Department of Veterans Affairs (VA) health-care system. VA Cooperative Study 420 is a randomized clinical trial of group psychotherapy for treating PTSD among veterans who sought VA care. Participants at ten sites were randomly assigned to receive one of the two treatments: active treatment that embedded exposure therapy in a group context or comparison treatment that avoided trauma focus and instead addressed current interpersonal problems. Treatment was delivered weekly to groups of six participants for 30 weeks, followed by five monthly booster sessions. Follow-up assessments were conducted at the end of treatment (7 months) and the end of boosters (12 months) for all participants. Long-term follow-up data were collected for a subset of participants at 18 and 24 months. The primary outcome is PTSD severity; other symptoms, functional status, quality of life, physical health, and service utilization also were assessed. Data analysis will account for the clustering introduced by the group nature of the intervention. The pivotal comparison was at the end of treatment. Analyses of subsequent outcomes will concentrate on the question of the durability of effects. The study provides an example of how to address the unique challenges posed by multisite trials of group psychotherapy through attention to methodological and statistical issues. This article discusses these challenges and describes the design and methods of the study. Control Clin Trials 2001;22:74-88