BACKGROUND Despite the uncertainty surrounding the safety of switching warfarin formulations, limited data exist on the resource use and costs associated with this switching pattern. OBJECTIVE To evaluate health care resource use and costs associated with switching warfarin formulations among patients with atrial fibrillation (AF) in a managed care organization. METHODS Patients diagnosed with AF (ICD-9 427.31) between July 2004 and August 2008 and who received warfarin therapy were identified in the HealthCore Integrated Research Database and categorized into 3 groups: users of generic warfarin formulations from a single drug manufacturer (generic-only group), users of branded warfarin formulations only (brand-only group), and patients who used generic and branded warfarin therapy interchangeably or who may have used generic drugs from 1 or more manufacturers (generic/brand switching group). Patients were followed 12 months or longer after their index warfarin prescription date to compare all-cause resource use and costs using multivariable regression analysis. RESULTS The analysis included 12,908 patients: 71.82% were in the genericonly group, 9.61% were in the brand-only group, and 18.57% were in the generic/brand switching group. Patients in the generic/brand switching group were more likely to be hospitalized (relative risk [RR] = 1.43, p < 0.0001) or to use emergency department services (RR = 1.20, p < 0.01), compared to the brand-only users. Hospitalizations were more likely (RR = 1.26, p < 0.001) to occur among generic-only users versus brand-only users. Adjusted mean pharmacy costs per member per month were lower in the generic/brand switching group compared to the brand-only group ($257 vs $273, p = 0.038), but inpatient costs were higher ($1250 vs $972, p < 0.001), resulting in higher ($2125 vs $1847, p < 0.001) total costs. Generic-only users had lower pharmacy costs compared to brand-only users ($246 vs $273, p < 0.001), but total health care costs trended to be higher in the generic-only group ($1957 vs $1847, p = 0.053). CONCLUSIONS The use of both generic and branded formulations of warfarin interchangeably, or the use of generics from more than 1 manufacturer, was associated with increased use of all-cause health care resources and total costs in patients with AF.