OBJECTIVES: In the management of atrial fibrillation (AF), warfarin has been the anticoagulant of choice for preventing thrombotic complications, however, its need for regular blood test monitoring has led to the development of alternatives such as dabigatran.  In order to address the variability and uncertainties in cost-effectiveness and budget impact across jurisdictions, a systematic review of economic analyses was conducted. METHODS: A systematic review was conducted of economic evaluations published to November 2011 evaluating the cost-effectiveness of dabigatran versus warfarin for stroke prevention in AF.  Databases searched included Ovid MEDLINE, EMBASE, the Cochrane Library and PubMed. The grey literature was also searched for relevant articles. For the purpose of a qualitative synthesis, details on the study design, data sources, cost effectiveness results (i.e. incremental cost effectiveness ratios (ICER)) were abstracted.  Key factors influencing the cost-effectiveness of dabigatran compared with warfarin across different countries and health systems were identified. RESULTS: Seven economic evaluations comparing dabigatran and warfarin from four countries were identified.  Costs, QALYs and ICERS were reported in all but one study.  ICERs for dabigatran compared to warfarin ranged from £4,879.17 to $152,142.86 US, depending on the dabigatran dose and currency.  Variations in ICERs occurred despite the fact that the efficacy and hemorrhage data were obtained from the same source, the RE-LY trial.  Key factors identified between the models for variability in the results included differences in the costs of managing AF across countries; assumptions regarding warfarin monitoring frequency and costs, and INR control (trial-like or real-world setting); incorporation of baseline risk in relative rates of adverse events; and the costs of treating dabigatran-related hemorrhages without an antidote. CONCLUSIONS: Economic analyses for dabigatran versus warfarin have produced widely varying results. Real world effectiveness and safety data, including warfarin management practices, are useful to inform cost-effectiveness in practice.