OBJECTIVES To examine hospitalization use and healthcare costs of elderly MDD patients treated with escitalopram compared to those treated with either generic SSRIs or SNRIs. METHODS Elderly MDD patients (age 65) initiated on escitalopram, a generic SSRI, or SNRIs were identified in the Ingenix Impact Database (2003-2007). Hospitalization rates, length of stay, and healthcare costs were examined over the 6-month period following therapy initiation (analysis period). Logistic and negative binomial regressions were used to compare the rate and days of hospitalization, respectively. Wilcoxon tests were used to compare costs descriptively. General Linear Model regression was conducted to control for patient characteristics including demographics, comorbidities, and baseline medical resource use. RESULTS A total of 1850 elderly patients initiated on escitalopram, 2668 on generic SSRIs, and 1053 on SNRIs. Escitalopram patients had higher comorbidities, healthcare utilization, and costs at baseline than generic SSRI and SNRI patients. Logistic regression showed that escitalopram patients were less likely to be hospitalized in the analysis period than generic SSRI (OR=0.81, P=0.0071) or SNRI patients (OR=0.88, P=0.1870). Negative binomial regression showed that escitalopram patients had fewer hospitalization days than generic SSRI (IRR=0.79, P=0.0416) and SNRI patients (IRR=0.74, P=0.0442), which translated into 54.0 and 70.6 more days per 100 patients for the generic SSRI and SNRI patients over 6 months, respectively. Escitalopram patients had a $3,758 cost reduction during the analysis period, significantly greater than the cost reductions for generic SSRI and SNRI patients of $951 and $562, respectively (both P<0.0001). GLM regression indicated that the 6-month risk-adjusted total healthcare costs for escitalopram patients were $985 (P=0.0758) and $1,889 (P=0.0080) lower than for generic SSRI and SNRI patients, respectively. CONCLUSIONS Compared to elderly MDD patients initiated on either generic SSRIs or SNRIs, patients initiated on escitalopram had significantly fewer hospitalization days and lower healthcare costs.