BACKGROUND: Mental health morbidity in post-conflict settings is high. Nevertheless, randomized controlled trials of psychotherapy on site are rare. Our aim was to integrate rigorous research procedures into a humanitarian programme and test the efficacy of resource activation (ROTATE) in treating post-traumatic stress disorder (PTSD), co-morbid symptoms and impaired functioning in Cambodia. METHOD: A total of 86 out-patients with PTSD were randomly assigned to five sessions of ROTATE (n = 53) or a 5-week waiting-list control (WLC) condition (n = 33). Treatment was provided by six Cambodian psychologists who had received extensive training in ROTATE. Masked assessments were made before and after therapy. RESULTS: PTSD remission rates according to the DSM-IV algorithm of the Harvard Trauma Questionnaire were 95.9% in ROTATE and 24.1% in the WLC condition. Thus, patients receiving ROTATE had a significantly higher likelihood of PTSD remission (odds ratio 0.012, 95% confidence interval 0.002-0.071, p < 0.00001). Additionally, levels of anxiety, depression and impaired functioning were significantly reduced compared with the WLC condition (p < 0.00001, between-group effect sizes d = 2.41, 2.26 and 2.54, respectively). No harms were reported. CONCLUSIONS: ROTATE was efficacious in treating Cambodian patients with high symptom levels of PTSD, emotional distress and impaired functioning. ROTATE is a brief, culturally adaptable intervention focusing on stabilization and strengthening resources rather than trauma confrontation. It can be taught to local professionals and paraprofessionals and enhance access to mental health care for patients in need.