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Introduction: Patients with non-valvular atrial fibrillation require anticoagulation therapy for prevention of thromboembolic events. The safest type of anticoagulation therapy regarding intracranial hemorrhage has not been established yet. Methods: We conducted a systematic review of literature in the time period 2011-2016 in databases (PubMed-EMBASE). We included meta-analysis, systematic reviews and randomized clinical trials addressing the molecules of interest (apixaban, dabigatran, edoxaban, rivaroxaban). We identified 512 articles, after which 14 studies were selected for the final analysis. Results: Through comparative evaluation of the four molecules in different doses versus warfarin, we found a decrease in intracranial hemorrhage in patients on therapy with novel anticoagulants, results support their usage in all of the articles included for analysis. However, when evaluating hemorrhage-related outcomes in different sub-populations, the results seem to have a smaller impact and in some cases they do not reach statistical significance, also, the benefit was reduced or disappeared. Conclusions: The results from this review can serve as useful tools in order to support physicians in the decision-making process regarding choice of the right type of anticoagulant therapy in specific clinical situations
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