OBJECTIVES: Compare health care costs of patients with post-traumatic stress disorder (PTSD) to those of patients with major depressive disorder (MDD) in U.S. Medicaid and privately-insured populations. METHODS: Patients with ≥2 PTSD diagnoses (ICD-9-CM: 309.81) on/after January 1, 1999 and ≥1 PTSD diagnosis on/after January 1, 2003 were identified from Medicaid claims data from Florida, Missouri, and New Jersey (1999-2007) and from a privately-insured claims database (1999-2008).  The index date was defined as the first PTSD diagnosis on/after 1/1/2003 that was not the first overall PTSD diagnosis.  PTSD patients had continuous eligibility for the 6-month baseline period before and 12-month study period following their index date and were ages 18-64 during the study period.  Potential MDD controls (ICD-9-CM: 296.2, 296.3) without PTSD diagnosis were identified using similar selection criteria.  MDD controls were matched to PTSD patients on age, gender, state/region, employment status, index year, and race (for Medicaid patients).  Study period direct costs, calculated as reimbursements in 2008 dollars to third-party payers for medical services and prescription drugs, were compared between PTSD patients and matched MDD controls using nonparametric bootstrapping. RESULTS: In the baseline period, PTSD patients had higher rates of other mental disorders (e.g. anxiety, bipolar disorder), and higher average direct costs than MDD controls both in the Medicaid and privately-insured populations.  Among Medicaid patients, PTSD patients also had lower average Charlson Comorbidity Index compared with MDD controls.  Average study period direct costs were higher for PTSD patients than MDD controls ($18,753 vs. $17,990 for Medicaid and $10,960 vs. $10,024 for privately-insured, both p<0.05).  The difference in direct costs was driven by higher mental health-related costs for PTSD patients than for MDD controls.  CONCLUSIONS: PTSD patients had approximately 4-10% higher direct costs in the 12-month study period compared to MDD controls driven by higher mental-health related direct costs.