Background: At present, a consistent and standardized method for evaluating the effectiveness and safety of anticoagulant treatment in such patients remains lacking. Objective: The purpose of this research was to assess the efficacy and safety of anticoagulant treatment for patients with sepsis. Methods: A comprehensive search was carried out on PubMed, Embase and Cochrane Library to identify Randomized Controlled Trials (RCTs) which compared the efficacy and safety of anticoagulants with placebo or no treatment in patients with sepsis. The reduction in 28/30-day all-cause mortality or the regression of disseminated intravascular coagulation (DIC) was regarded as effective, while bleeding complications constituted the most prevalent adverse events. Results: A sum of 19 RCTs encompassing 8,177 patients were incorporated. In all sepsis patients, the anticoagulant group exhibited an 8% decrease in the death risk when contrasted with the placebo group. The combined relative risk [RR] was 0.92 (with a 95% confidence interval [CI] of 0.86 - 0.98; P = 0.02). Anticoagulant therapy might potentially reduce patient mortality (RR 0.87, 95% CI 0.62 - 1.22, P = 0.42) and enhance the regression rate of DIC (RR 1.62, 95% CI 1.32 - 2, P < 0.00001) in 6 studies with a baseline of DIC. Nevertheless, the employment of anticoagulants augmented the bleeding risk in patients (RR 1.31, 95% CI 1.16 - 1.49, P < 0.0001). Conclusion: The research discovered that anticoagulant treatment lessened the mortality rate among patients with sepsis and enhanced the regression of DIC in those patients with sepsis - associated DIC.