OBJECTIVES: This study examined real-world estimates of healthcare utilization and costs of newly diagnosed depressed patients following their initial depression diagnosis compared to an age- and gender-matched cohort without depression. METHODS: A cohort of patients with a depression diagnosis (ICD-9-CM 296.2, 296.3, 298.0, 300.4, 309.0, 309.1, 309.28, or 311) in 2006 and an age- and gender-matched comparator cohort were extracted from the Thomson Reuters MarketScan® database.  The index date for each patient was the date of initial depression diagnosis. Comparator patients were randomly assigned an index date. Study subjects were required to be free of depression with no evidence of antidepressant use for 1 year prior to their index date. The study period began at the index date and continued until either the last day of the study period, December 31, 2008, or earlier if the patient was lost to follow-up. Medical care utilization and costs were assessed for the depressed and comparator cohorts. RESULTS: A total of 175,092 patients with diagnosed depression were included in the analysis. Total utilization (sum of visits plus prescriptions) was approximately 2.1-fold greater among depressed patients than among the comparator cohort (34.3 vs. 16.2 per patient-year), a difference driven by outpatient visits (17.56 vs. 6.58 per patient-year). Total health care costs for the depressed cohort were more than 2.7-fold greater than for the comparator cohort ($10,840 vs. $3,980 per patient-year). Results were consistent throughout virtually all major utilization and prescription dispensing categories and generally increased with increasing age.  Follow-up utilization and costs for comparators were similar to baseline (15.6 and $3,420 at baseline), whereas these metrics increased 40% and 58% (24.5 and $6,840 at baseline) for depressed patients following their depression diagnosis. CONCLUSIONS: Compared to age- and gender-matched depression-free comparators, depressed patients had substantially higher health care utilization and costs.