Vitamin K antagonists are used as a temporary anticoagulation method after bioprosthetic valve replacement or repair. However, the novel direct oral anticoagulants may be a preferred method of anticoagulation because of their improved patient compliance. This meta-analysis aimed to evaluate the safety of direct oral anticoagulants versus vitamin K antagonists after biological valve replacement or repair. A systematic review and meta-analysis were performed for studies reporting the effect of direct oral anticoagulants versus vitamin K antagonists after biological valve replacement or repair. The inclusion criteria were studies of adults undergoing bioprosthetic mitral or aortic valve replacement or repair, comparing direct oral anticoagulants versus vitamin K antagonists in the early postoperative period. The main outcomes were thromboembolic and bleeding events, and short- and mid-term death rates. Six observational studies and one randomized controlled trial were included, with a total of 2994 direct oral anticoagulant recipients and 16,894 vitamin K antagonist recipients. There were no significant differences between the groups in terms of thromboembolic events (odds ratio: 0.82, 95% confidence interval: 0.45–1.49; P = 0.52) or bleeding events (odds ratio: 0.89, 95% confidence interval: 0.70–1.14, P = 0.36). Higher 30-day and mid-term death rates were observed in patients receiving direct oral anticoagulants, but this analysis was reported inconsistently, and was heavily influenced by a single study. In a mixed population of individuals undergoing bioprosthetic valve replacement or repair, there was no statistically significant difference between direct oral anticoagulants and vitamin K antagonists in terms of reducing thromboembolic or bleeding events. Further studies are needed to establish the optimal anticoagulation regimen in this context.