Background: Cancer patients are at increased risk for venous thromboembolism (VTE) due to cancer-induced hypercoagulability. However, current guidelines do not routinely recom-mend prophylactic use of oral anticoagulants to prevent VTE in cancer patients. Objective: To evaluate the efficacy and safety of novel oral anticoagulants (NOACs) versus no anticoagulant use (no-use) and, additionally, differential effects between NOACs and warfarin, in VTE and adverse bleeding prevention among cancer patients, in consideration of risk stratification by gender, high-risk chemotherapy exposure, and Khorana index. Methods: This national health insurance data-based study with a 180-day follow-up enrolled cancer patients with or without oral anticoagulant use in 2017. The primary outcome was VTE risk in oral anticoagulant users vs non-users. Four propensity score-matched comparison pairs were designed: use vs no-use, NOAC vs no-use, warfarin vs no-use, and NOAC vs warfarin. A logistic regression model was used to investigate between-group differences in VTE and bleeding risk. Results: When compared to no-use, NOACs showed substantial effects in preventing VTE complications (OR=0.40, p<0.001), primarily deep vein thrombosis (DVT) events (OR=0.38, p<0.001), in both male and female cancer patients as well as those with a Khorana score ≥1. Adverse bleeding risk was comparable or lower in NOAC-receiving female patients (p=0.13) and male patients (p=0.04), respectively. In contrast, no protective effects were found with warfarin compared to no-use in controlling thrombosis and adverse bleeding risk. In a head-to-head comparison of NOACs versus warfarin, DVT risk in those patients exposed to high-risk chemotherapy was significantly decreased with NOAC use (OR=0.19, p=0.03). Conclusion: NOACs can be a promising thromboprophylactic option in both male and female cancer patients with VTE risk.