OBJECTIVES: Evaluate health care utilization among depressed patients before and after initiating duloxetine. METHODS: Depressed adults treated with duloxetine during January 1, 2006-September 30, 2007 were identified from the General Practice Research Database. All-cause health care utilization in the 12-months before and after treatment initiation was compared for patients and for the subset of patients with pre-period unexplained pain (UPain). Generalized Estimating Equation models were used to identify factors associated with the pre-post differences in hospitalization rates. Covariates included age, gender, pre-period comorbid conditions and medication use. RESULTS: A total of 909 patients were identified (mean age=49.6; female=67.7%), and 45% experienced UPain. Three-quarters of patients were prescribed a SSRI and 11% were untreated with antidepressants before initiating duloxetine.  Among  patients, the rate of hospitalization was higher in the pre-period compared to the post-period (20.7% vs.16.5%, p=0.006). There were no significant pre-post differences in the rates of accident & emergency visits, specialist referrals, or analgesic use. Among patients with UPain, fewer were hospitalized (26.2% vs. 19.1%, p=0.003) or received analgesic in the post-period (77.0% vs. 71.7%, p=0.015). Multivariate analysis confirmed fewer patients experienced hospitalization after duloxetine initiation.  All depressed patients with pre-period anxiolytic use (OR=0.70, 95% CI, 0.50-0.97, p=0.033) or UPain patients with pre-period anticonvulsant use (OR=0.44, 95% CI, 0.21-0.91, p=0.026) experienced a decreased hospitalization rate after initiating duloxetine and the magnitude of change was larger than that for patients not  receiving these medications.  All depressed patients with pre-period alcohol/drug dependence (OR=1.83, 95% CI, 1.01-3.30, p=0.045) and sleep disorder (OR=1.65, 95% CI, 1.05-2.59, p=0.031) had an increase in the hospitalization rate from the pre- to post-period, while those without the conditions had a decreased hospitalization rate. CONCLUSIONS: Hospitalization rates were lower following duloxetine initiation among depressed patients. Pre-period alcohol/drug dependence, sleep disorders, anxiolytic and anticonvulsant use were associated with the pre-post difference in the hospitalization rate.