Objective: Docosahexaenoic acid (DHA) might help prevent or attenuate posttraumatic stress disorder (PTSD) symptoms. We examined the efficacy and safety of DHA for preventing PTSD (DSM-IV) after severe accidental injury.Method: From December 2008 to August 2013, we conducted a randomized, double-blind, placebo-controlled trial of 110 accident-injured patients consecutively admitted to an intensive care unit of the National Disaster Medical Center in Tokyo, Japan. All patients were taught about their psychological reactions to accidental injury for 20 minutes and were randomly assigned to receive 1,470 mg/d of DHA plus 147 mg/d of eicosapentaenoic acid (EPA; n = 53) or placebo (n = 57) for 12 weeks. The primary outcome was total score on the Clinician-Administered PTSD Scale (CAPS) at 3-month follow-up. Secondary outcomes included PTSD diagnosis (full-blown or partial PTSD). Adherence to the interventions was assessed by erythrocyte fatty acid composition.Results: At 3 months, the CAPS total score revealed no differences between the 2 groups (10.78 in the DHA group vs 9.22 in the placebo group; n = 100; P = .572). We found that 11.1% of the DHA group and 5.5% of the placebo group developed PTSD. The erythrocyte level of DHA and EPA in the DHA group was significantly elevated compared to the placebo group (P < .01).Conclusions: Docosahexaenoic acid supplementation was not superior to placebo for the secondary prevention of PTSD symptoms at 3 months after severe accidental injury. The efficacy of a different ratio of DHA and EPA and higher doses of omega-3 fatty acids as secondary prevention of PTSD remains to be determined. (C) Copyright 2015 Physicians Postgraduate Press, Inc.