Simple SummaryCancer and atrial fibrillation share an enhanced bleeding and thrombotic risk, nevertheless in cancer populations optimal anticoagulation regiments are yet to be validated. This meta-analysis aimed to gather the currently available evidence addressing the use of DOACs in atrial fibrillation cancer patients compared to Warfarin. In the oncological population, DOACs confer benefits in terms of stroke, major and minor bleeding, and thrombotic events, although prospective studies are awaited to strengthen the body of evidence currently available.Abstract(1) Introduction: Cancer and atrial fibrillation (AF) are increasingly coexisting medical challenges. These two conditions share an increased thrombotic and bleeding risk. Although optimal regimens of the most suitable anti-thrombotic therapy are now affirmed in the general population, cancer patients are still particularly understudied on the matter; (2) Aims And Methodology: This metanalysis (11 studies (incl. 266,865 patients)) aims at evaluating the ischemic-hemorrhagic risk profile of oncologic patients with AF treated with oral anticoagulants (vitamin K antagonists vs. direct oral anticoagulants); (3) Results: In the oncological population, DOACs confer a benefit in terms of the reduction in ischemic, hemorrhagic and venous thromboembolic events. However, ischemic prevention has a non-insignificant bleeding risk, lower than Warfarin but significant and higher than the non-oncological patients; (4) Conclusions: Anticoagulation with DOACs provides a higher safety profile with respect to VKAs in terms of stroke reduction and a relative bleeding reduction risk. Further studies are needed to better assess the optimal anticoagulation strategy in cancer patients with AF.