OBJECTIVES: To assess differences in healthcare costs associated with initiation of asenapine versus aripiprazole among patients with bipolar disorder (BD).  METHODS: We used two large US healthcare claims databases that collectively included commercially insured patients aged <65 years and Medicare enrollees to identify all adults (≥18 years) with BD  (ICD-9-CM diagnosis codes 296.0X, 296.1X, 296.4X, 296.6X, 296.7X, 296.80, 296.81, 296.89) who began therapy with asenapine or aripiprazole between 2009 and 2012.  Patients without continuous enrollment for the 6-month periods before and after the date of the first prescription claim for asenapine or aripiprazole (“index date”) were excluded. Asenapine patients were then matched to aripiprazole patients using propensity scoring to control for differences between the groups.  HRU and associated costs (2012 dollars) were deemed BD-related based on the presence of a BD diagnosis code on the relevant claim.  Within each group, differences in BD-related HRU and costs  were estimated between the pre- and post- index periods, and then compared across groups. RESULTS: A total of 2680 patients were included in the analyses (n=1,340 for each group); the groups were comparable  with respect to age (mean age: 42.8 years for asenapine patients vs. 42.2 years for aripiprazole patients, p=0.27), percent female (70.3% vs. 70.1%, p=0.90), and Charlson comorbidity index (mean: 0.45 vs. 0.42, p=0.55).  Asenapine patients had nearly a twofold greater decrease in total BD-related healthcare costs than aripiprazole patients (mean: -$863 for asenapine vs. -$490 for aripiprazole, p<0.05); BD-related outpatient costs also exhibited a significant decrease ($-2 vs. a $10 increase for aripiprazole patients, p<0.05). While pharmacy costs increased in both groups, the increase was significantly lower among asenapine patients ($886 vs. $1,518, p<0.05). CONCLUSIONS: As compared with aripiprazole, asenapine was associated with a reduction in total healthcare costs related to BD during the 6-month period following therapy initiation.