Background/Aim: There is almost no study on direct oral anticoagulant (DOAC) for the treatment of venous thromboembolism (VTE) in Japanese patients with advanced cancer. The aim of this study was to evaluate the efficacy of DOAC for the treatment of VTE in Japanese patients with advanced cancer. Methods: We retrospectively reviewed patients with active cancer who had new-onset proximal deep vein thrombosis and/or pulmonary embolism at our hospital. We compared two DOACs, edoxaban and apixaban, with warfarin and evaluated the incidence of VTE recurrence and bleeding in a period of 3 months. The recurrence was diagnosed based on computed tomography or echography findings. Results: The number of patients treated with edoxaban, apixaban, and warfarin was 47, 31, and 30, respectively. In the warfarin group, the mean international normalized ratio of prothrombin time (2SD) after 3 months was 2.11 (0.42). There was no incidence of major bleeding. Non-major bleeding occurred in 17%, 10%, and 27% of the patients treated with edoxaban, apixaban, and warfarin, respectively (edoxaban vs. warfarin, risk ratio [RR]: 0.64, 95% confidence interval [CI]: 0.27–1.52; apixaban vs. warfarin, RR: 0.38, 95% CI: 0.11–1.28). All bleeding episodes occurred in 30%, 26%, 57% of patients treated with edoxaban, apixaban, and warfarin, respectively (edoxaban vs. warfarin, RR: 0.53, 95% CI: 0.31–0.90; apixaban vs. warfarin, RR: 0.46, 95% CI: 0.23–0.89). Recurrent VTE in edoxaban, apixaban, and warfarin groups occurred in 8%, 3%, and 16% of the patients, respectively (edoxaban vs. warfarin, RR: 0.52, 95% CI: 0.18–2.18; apixaban vs. warfarin, RR: 0.22, 95% CI: 0.03–1.80). Fisher’s exact test was used for statistical analysis. Conclusion: Our study suggests that the DOAC groups are relatively at a lower risk of VTE recurrence, non-major bleeding, as well as all bleeding episodes, as compared with the warfarin group. Therefore, DOAC might be useful in the treatment of VTE in Japanese patients with advanced cancer.