| Summary: | <b>Background and aim</b>. Cancer and atrial fibrillation (AF) may be associated, and anticoagulation, either with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), is necessary to prevent thromboembolic events by reducing the risk of bleeding. The log incidence rate ratio (IRR) and 95% confidence interval were used as index statistics. Higgin’s I<sup>2</sup> test was adopted to assess statistical inconsistencies by considering interstudy variations, defined by values ranging from 0 to 100%. I<sup>2</sup> values of less than 40% are associated with very low heterogeneity among the studies; values between 40% and 75% indicate moderate heterogeneity, and those greater than 75% suggest severe heterogeneity. The aim of this meta-analysis was to compare the safety and efficacy of VKAs and DOACs in oncologic patients with AF. <b>Methods</b>. A meta-analysis was conducted comparing VKAs to DOACs in terms of thromboembolic events and bleeding. A meta-regression was conducted to investigate the differences in efficacy and safety between four different DOACs. Moreover, a sub-analysis on active-cancer-only patients was conducted. <b>Results</b>. A total of eight papers were included. The log incidence rate ratio (IRR) for thromboembolic events between the two groups was −0.69 (<i>p</i> < 0.005). The meta-regression did not reveal significant differences between the types of DOACs (<i>p</i> > 0.9). The Log IRR was −0.38 (<i>p</i> = 0.008) for ischemic stroke, −0.43 (<i>p</i> = 0.02) for myocardial infarction, −0.39 (<i>p</i> = 0.45) for arterial embolism, and −1.04 (<i>p</i> = 0.003) for venous thromboembolism. The log IRR for bleeding events was −0.43 (<i>p</i> < 0.005), and the meta-regression revealed no statistical difference (<i>p</i> = 0.7). The log IRR of hemorrhagic stroke, major bleeding, and clinically relevant non-major bleeding between the VKA and DOAC groups was −0.51 (<i>p</i> < 0.0001), −0.45 (<i>p</i> = 0.03), and 0.0045 (<i>p</i> = 0.97), respectively. Similar results were found in active-cancer patients for all the endpoints except for clinically-relevant non-major bleedings. <b>Conclusions</b>. DOACs showed better efficacy and safety outcomes than VKAs. No difference was found between types of DOACs.
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