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Background: Little is known about the economic burden for ischemic stroke (IS) patients with atrial fibrillation (AF) in China., Aim: We aimed to compare the economic burden of treatment-related costs in IS patients with AF vs. without AF in China., Methods: This retrospective analysis used economic burden data from the Beijing urban health insurance database. Using a random sampling method, 10% of the patients diagnosed with IS from 1 January through 31 December 2012 were enrolled. First hospitalization was considered as the index event and hospital utilization after the index event was followed up until September 2013. Overall healthcare cost during the study period was analyzed., Results: In 4061 patients with IS (mean ± SD age, 68.45 ± 13.95 years; AF: 992; without AF: 3069), the AF group had a higher percentage of patients with co-morbidities at baseline. Compared with the non-AF group, the AF group had significantly greater hospitalization at the index event (p < .001). Overall inpatient cost per patient during the observational period (Renminbi (RMB) 141,875.9 ± 121,071.8 vs. RMB 53,834.03 ± 63,535.72, in 2012 terms), total healthcare cost per patient (RMB 163,550.4 ± 131,103.5 vs. RMB 64,735.41 ± 67,584.95), total healthcare cost covered by health insurance, and annualized total healthcare cost per patient were higher in the AF group than in the non-AF group (p < .001). Treatment costs were significantly associated with old age, male gender, AF, and frequency of outpatient visits and hospitalization., Conclusions: AF increased the use of healthcare resources, treatment cost, and economic burden in patients with IS. Therefore, prevention of cardio-embolic events in patients with AF by anticoagulants may decrease the economic burden in patients with IS.