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Objective: To compare healthcare costs and resource utilization among patients with post-traumatic stress disorder (PTSD) vs control subjects with major depressive disorder (MDD) in populations covered by Medicaid or private insurance., Study Design: Retrospective analysis of Medicaid and private insurance administrative claims data., Methods: Patients with at least 2 PTSD diagnoses during or after 1999, and at least 1 PTSD diagnosis during or after 2003, were identified from deidentified Medicaid claims from Florida, Missouri, and New Jersey (1999-2007) and from a privately insured claims database (1999-2008). Patients had continuous eligibility 6 months before (baseline) and 12 months after (study period) the index date and were aged 18 to 64 years. Potential control subjects having MDD without PTSD diagnosis were identified using similar selection criteria. Control subjects with MDD were matched to patients with PTSD on age, sex, state or region, employment status (private insurance only), index year, and race/ethnicity (Medicaid only). Study period per-patient utilization and costs, calculated as reimbursements to providers for medical services and prescription drugs, were compared using univariate and multivariate analyses., Results: Patients with PTSD had higher rates of other mental health disorders (eg, anxiety and bipolar disorder) and higher mental health-related resource use and costs than control subjects with MDD in both Medicaid and privately insured populations. The mean study period total direct healthcare costs were higher for patients with PTSD than for control subjects with MDD ($18,753 vs $17,990 for Medicaid and $10,960 vs $10,024 for private insurance, P <.05 for both). The difference in total direct costs was driven by higher mental health-related resource use for patients with PTSD., Conclusion: Patients having PTSD had 4.2% to 9.3% higher mean annual per-patient healthcare costs compared with matched control subjects having MDD among patients covered by Medicaid or private insurance.