OBJECTIVES: To conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF). METHODS: We searched Medline, Embase, NHSEED and HTA databases and the Tuft’s Registry through October 10, 2012. Included models were cost-effectiveness analyses of newer agents for SPAF using a Markov or discrete event simulation model and published in English. RESULTS: Eighteen models were identified. Each was based on a lone randomized trial per new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150mg, 110mg and sequential dosing were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from the United States (44%), European countries (39%) and Canadian (17%) perspectives.   In base-case analyses, patients typically were at moderate-risk of stroke, initiated anticoagulation at 65-73 years of age, and were followed for/near a lifetime.  All models reported cost/quality-adjusted life-year, and while 22% reported using a societal perspective, no model included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER) for a newer anticoagulant (dabigatran 110mg (n=4)/150mg (n=2); rivaroxaban (n=1)) versus warfarin above commonly reported willingness-to-pay thresholds. ICERs (2012US$) versus warfarin ranged from $3,547-$86,000 for dabigatran 150mg, $20,713-$150,000 for dabigatran 110mg, $4,084-$21,466 for sequentially-dosed dabigatran and $23,065-$57,470 for rivaroxaban. Apixaban was demonstrated to be economically-dominant compared to aspirin, and dominant or cost-effective ($11,400-$25,059) versus warfarin.  Based on indirect comparisons, 3 models compared the cost-effectiveness of new agents and reported conflicting results. CONCLUSIONS: Cost-effectiveness models of newer anticoagulants for SPAF have been extensively published.  They frequently found newer anticoagulants to be cost-effective, but due to the lack of head-to-head trials and the heterogeneity in clinical characteristic of underlying trials and modeling methods, it is currently unclear which of these newer agents is most cost-effective.