OBJECTIVES: To compare the health care costs and utilization of adult major depressive disorder (MDD) patients treated with escitalopram to those treated with other SSRI/SNRI. METHODS: MDD patients (age =18) initiated on escitalopram or other SSRI/SNRI were identified in the IHCIS National Managed Care Database (2003–2005). Health care costs and resource use of patients on escitalopram were compared to patients on other antidepressants over the 6 months following therapy initiation (study period). Wilcoxon tests were used to compare costs descriptively. GLM regressions with log link function were used for cost comparison. Two-part regression models were used to deal with zero cost. Logistic regressions were used to compare 6-month rates of hospitalization, emergency visit, and substance abuse. Negative binomial regressions were used to compare the number of hospitalization days and emergency visits. All regressions adjusted for patient demographics, comorbidities, and baseline medical resource use. Costs were inflation adjusted to 2005 US dollars. RESULTS: The study sample included 10,465 MDD patients initiated on escitalopram and 28,310 patients initiated on other SSRI/SNRI. Descriptive analyses showed that escitalopram patients had on average $753 lower 6-month total health care costs than patients on other SSRI/SNRI (p<0.0001), with more than half of the difference from lower hospitalization costs ($394, p<0.0001). GLM regressions showed that escitalopram patients cost $839 less (p<0.0001) in total health care costs and $405 less (p<0.01) in inpatient costs. Medical resource utilization regressions showed that, compared to patients on other SSRI/SNRI, patients on escitalopram were less likely to have hospitalization (p=0.0001), emergency visit (p<.0001), and substance abuse (p=0.001). Escitalopram patients had 31% fewer hospitalization days (p<0.0001) and 15% fewer emergency visits (p<0.0001). CONCLUSION: Compared to adult MDD patients initiated on other SSRI/SNRI, patients on escitalopram have lower health care costs and utilize fewer medical resources.