OBJECTIVE: An estimated 50% of Americans are exposed to at least one traumatic event in a lifetime. Of those, 20% experience post-traumatic stress disorder (PTSD). Approximately 50% of patients with PTSD have comorbid major depression disorder. This study examined the cost differential between patients with major depressive disorder (MDD) only, PTSD only and patients with comorbid MDD and PTSD. METHODS: A retrospective study of patients with MDD and PTSD was performed using 1996 to 1999 claims from the MarketScan Database, with private sector health data from approximately 100 payers. Three cohorts of patients were created: 1) patients with MDD (ICD-9-CM 296.2, 296.3, 300.4, or 311), 2) patients with PTSD (ICD-9-CM 309.81), and patients with both MDD and PTSD. Patients had to also have a prescription drug claim for an antidepressant within 30 days of diagnosis. During the 6 month follow-up, healthcare utilization and expenditures for inpatient, outpatient, emergency room, and outpatient drugs were calculated. Total expenditures were compared. ANOVA was used to assess the statistical significance of differences in expenditures. RESULTS: A total of 24,955 patients with fee-for-service health coverage were identified . Of those, 24,156 were diagnosed with MDD, 196 with PTSD, and 603 had co-occurring MDD and PTSD. The mean total expenditure for patients with MDD, PTSD, and MDD with PTSD were $3,407, $3,714, $5,723 respectively (p<0.05). PTSD was significantly associated with increased expenditures after stratifying for gender, age, and geographic region. CONCLUSION: Costs associated with MDD and PTSD are substantial. The total health care expenditures of patients with PTSD were significantly higher than expenditures for patients with MDD alone. Patients with comorbid depression and PTSD had significantly increased expenditures than patients with one condition.