Objective. Open label trials of divalproex in the treatment of posttraumatic stress disorder (PTSD) show positive results. The objective of this study was to examine the therapeutic effects of divalproex in a larger naturalistic sample of patients with PTSD. Methods. A retrospective analysis was performed on 325 veteran charts identified through a computerized search of PTSD diagnosis matched with pharmacy records (any form of divalproex). The medication names, doses, labs, and dates (except for the divalproex index visit) were blackened. An investigator blinded to the order of visits and blackened information rated the progress notes preceding and following psychopharmacological intervention with divalproex with the Clinical Global Impression Scale for Improvement (CGI-I). Results. Fifty patients met eligibility criteria. Three were treated with divalproex monotherapy and 47 were treated adjunctively. The improved endpoint CGI-I differed significantly from "no change" (P <0.000001). Twenty-five (50%) were rated as very much or much improved on the CGI-I. Patients treated in primary care had a greater improvement compared to those in the mental health setting (P <0.005). Divalproex dosage and serum valproic acid levels (n = 37) were well correlated (r = 0.57, P <0.0005). Conclusion. Divalproex treatment improves the global clinical function of veterans with PTSD. Further controlled study is warranted. © 2005 Taylor & Francis.