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Background: Patients with non-valvular atrial fibrillation (NVAF) use oral anticoagulants (OACs) to decrease their risk of stroke; however, taking OACs may also increase their risk of bleeding.Objective: To assess long-term healthcare costs related to ischemic stroke/systemic embolism (SE) and major bleeding events in patients with NVAF treated with non-vitamin K antagonist oral anticoagulants (NOACs).Methods: Clinformatics™ Data Mart database from 1/2009-12/2016 was analyzed. Patients aged ≥18 with ≥1 ischemic stroke or SE hospitalization claim (index date) were matched 1:1 to patients without a stroke based on propensity scores. Patients with a major bleeding event identified using a validated algorithm (Cunningham et al., 2011) were similarly matched to patients without major bleeding. A randomly selected index date was imputed for patients without an event. All patients had a dispensing of a NOAC agent overlapping with the index date, had ≥12 months of eligibility pre-index date and ≥1 NVAF diagnosis. Healthcare costs were calculated from index date until the earliest date of death, switch to warfarin, end of insurance coverage or end of data availability. Mean costs were evaluated at 1, 2, 3 and 4 years using Lin’s method (Kaplan-Meier product-limit estimator, accounting for death) and compared using non-parametric bootstrap procedures.Results: The additional cost of care for patients with vs. without ischemic stroke/SE were $48,822, $50,418, $56,721 and $59,354 at 1, 2, 3 and 4 years, respectively (Table; p<.0001 for all comparisons). The additional cost of care for patients with vs. without major bleeding at 1, 2, 3 and 4 years were $30,990, $35,443, $43,685 and $46,662, respectively (p<.0001 for all comparisons).Conclusions: Patients experiencing an ischemic stroke/SE or major bleeding event incur higher healthcare costs than those patients that do not, and the all-cause costs associated with ischemic stroke/SE appeared higher than major bleeding.