A systematic review and meta-analysis was conducted to investigate the effects of computerized guideline-oriented clinical decision support system (CDSS) on antithrombotic therapy in patients with atrial fibrillation. PubMed, the Cochrane Library, and Web of Science were queried. Four studies were included in this meta-analysis. The proportion of appropriate antithrombotic therapy in accordance with clinical guidelines was significantly higher in the CDSS group than in the control group (risk ratio (RR): 1.03, 95% confidence interval (CI): 1.01 to 1.04, P = 0.004). Although the incidence of thromboembolic events was similar between the two groups (RR: 1.12, 95% CI: 0.88 to 1.42, P = 0.357), the incidence of major bleeding tended to be lower in the CDSS group compared with the control group (RR: 0.79, 95% CI: 0.61 to 1.01, P = 0.063). Computerized guideline-oriented CDSS may be effective for appropriate antithrombotic therapy as compared with control in patients with atrial fibrillation.