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Objectives: We sought to determine the impact of stroke and major bleeding excluding intracranial hemorrhage (MB) events on healthcare costs in a real-world nonvalvular atrial fibrillation (NVAF) population. Methods: Healthcare claims data from U.S. commercial and Medicare health plans were used to identify beneficiaries with NVAF during 2008-2012. Patients were classified into cohorts according to event type (No event, Stroke only, MB only, or Stroke plus MB). All-cause total healthcare costs and inpatient costs related to stroke and MB were calculated during 1-year period following the index date (date of initial event or first qualifying AF claim for No event group). Inpatient hospitalizations related to events were identified using ICD-9-CM diagnosis codes. Costs were standardized to 2012 US dollars. Results: Of the 40,654 patients included in the study, 28% had events (8.9% Stroke only, 14.5% MB only, and 4.7% Stroke plus MB). Relative to the No event cohort, all-cause unadjusted per-patient per-month (PPPM) total costs were $4,669 higher for Stroke only and $4,160 for MB only. For Stroke plus MB patients, unadjusted all-cause PPPM total costs were $6,322 higher compared to the No event cohort. Among Stroke only and MB only patients, the economic burden of hospitalizations related to MB (57% of total costs) was similar to Stroke only (63% of total costs). Hospitalizations related to stroke or MB accounted for 65% of total costs for Stroke plus MB. Conclusions: NVAF patients who have a stroke or MB event incur higher healthcare costs relative to patients without events. Interventions preventing stroke or MB events have the potential to reduce the healthcare burden associated NVAF.