Background: Optimal treatment regimen for patients with cancer-associated venous thromboembolism (CA-VTE) remain unclear. Therefore, we sought to compare the outcomes of (VKAs) versus direct apixaban and low molecular weight heparin (LMWH) in patients with CA-VTE. Methods: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies comparing efficacy and safety of apixaban and LMWH in patients with CA-VTE. Major bleeding, clinically relevant non major bleeding (CRNMB), recurrence of pulmonary embolism (PE), deep venous thrombosis (DVT) and bleeding related mortality were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95 percent confidence intervals (CIs). Results: The analysis included 12011 patients from 3 RCTs and 2 observational studies. Compared to LMWH, apixaban significantly decreased the risk of major bleeding (RR 0.67 [95% CI 0.54, 0.83]; P=0.0003, I2=0%) without significantly changing the risk of clinically relevant non major bleeding (RR 0.96 [95% CI 0.64, 0.1.45]; P=0.85, I2=57%). Patients on apixaban had a noticeably reduced the risk of recurrence of PE than those taking LMWH, according to a meta-analysis (RR 0.56 [95% CI 0.32, 0.99]; P=0.05, I2=0%). There was no discernible difference between apixaban and LMWH in bleeding related mortality events (RR 0.20 [95% CI 0.01, 4.18]; P=0.30, I2=NA%), and recurrence of DVT (RR 0.60 [95% CI 0.22, 1.59]; P=0.23, I2=32%), Conclusion: Due to its lower risk of severe bleeding and reduced PE recurrence, apixaban may be a preferable treatment option for CA-VTE, but additional research is required to validate these conclusions and evaluate its long-term efficacy and safety.