OBJECTIVES: To examine differences in healthcare resource use (HRU) and cost among patients with schizophrenia initiating therapy with asenapine versus other branded atypical antipsychotics (“OBAP”) (i.e., aripiprazole, lurasidone, iloperidone, paliperodone).  METHODS: Using two large US healthcare claims databases—one of commercially insured patients aged <65 years and one of Medicare enrollees—we identified all adult patients (≥18 years) with schizophrenia (ICD-9-CM 295.XX) initiating treatment with asenapine versus OBAP between 2009 and 2012.  All patients were required to be continuously enrolled for the 6-month periods before and after the date of the first prescription claim for asenapine or OBAP (this was deemed the “index date”). We used propensity-score matching to control for differences between the groups. Changes in HRU and costs (2012 dollars) between the 6 month pre- and post-index periods were calculated within each group and then compared across groups. RESULTS: A total of 259 asenapine patients were propensity matched to an equal number of OBAP patients; matched groups were similar in terms of age (mean: 39.9 years for asenapine patients vs. 41.8 years for OBAP patients, p=0.19), gender (58.7% vs. 56.8% female; p=0.66); and Charlson comorbidity index (mean: 0.47 vs. 0.52, p=0.65).  Differences in HRU between the pre- and post-index periods nominally favored asenapine patients, including greater reductions in admissions (mean: -0.49 for asenapine patients vs. -0.40 for OBAP patients, p=0.38) and emergency room visits (-0.19 vs. -0.08, p=0.26); decreases in total healthcare costs also favored asenapine patients ($-7,609 vs. $-5,585, p=0.45).  While pharmacy costs increased in both groups, the increase was significantly lower among asenapine patients ($922 vs. $1,707, p<0.05).  CONCLUSIONS: Initiation of asenapine for schizophrenia is associated with significantly lower pharmacy costs than OBAP, and nominally greater decreases in levels of HRU and total healthcare costs.