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The safety and efficacy of direct oral anticoagulants in cancer patients is currently unclear. Low-molecular-weight heparin remains the standard of care for cancer patients with venous thromboembolism, with warfarin, a vitamin K antagonist, as an alternative. Clear recommendations do not exist for patients with both active cancer and non-valvular atrial fibrillation. The objectives of this study were to report safety and efficacy outcomes of direct oral anticoagulants, low-molecular-weight heparin, and vitamin K antagonist in cancer patients with venous thromboembolism or non-valvular atrial fibrillation. Retrospective chart review of adult cancer patients from 2012 to 2015 who received an antineoplastic agent and an anticoagulant. A total of 258 patients were reviewed: 80 patients in direct oral anticoagulant group, 95 patients in low-molecular-weight heparin group, and 83 patients in vitamin K antagonist group. Sixty-seven percent of patients were on an anticoagulant for acute or chronic venous thromboembolism. Major bleeding events were similar across the groups (15% direct oral anticoagulant vs 17% low-molecular-weight heparin vs 18% vitamin K antagonist). The most common type of major bleeding event was gastrointestinal bleeding. A total of five fatal bleeding events occurred. Venous thromboembolism recurrence rates were higher in both direct oral anticoagulant (18%) and low-molecular-weight heparin (12%) groups while lower in vitamin K antagonist group (10%) compared to previous studies. Cancer patients receiving direct oral anticoagulants, low-molecular-weight heparin, or vitamin K antagonist had similar rates of major bleeding events, with gastrointestinal bleeding being the most common event. Venous thromboembolism recurrence rates were higher in direct oral anticoagulant and low-molecular-weight heparin groups than prior studies. Randomized trials are warranted to establish clear safety and efficacy in this population