Treatment of splanchnic vein thrombosis (SVT) is challenging and evidence to guide therapeutic decisions remains scarce. The objective of this systematic review and meta-analysis was to determine the efficacy and safety of anticoagulant therapy for SVT. MEDLINE, EMBASE, and Clinicaltrial.gov were searched from inception up to December 2019 without language restrictions to include observational studies and randomized controlled trials reporting radiological or clinical outcomes in patients with SVT. Pooled proportions and risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random-effects model. Of 4312 records identified by the search, 97 studies including 7969 patients were analyzed. In patients receiving anticoagulation, the rates of SVT recanalization, SVT progression, recurrent VTE, major bleeding, and overall mortality were 58% (95% CI, 51-64), 5% (95% CI, 3-7), 11% (95% CI, 8-15), 9% (95% CI, 7-12), and 11% (95% CI, 9-14), respectively. The corresponding values in patients without anticoagulation were 22% (95% CI, 15-31), 15% (95% CI, 8-27), 14% (95% CI, 9-21), 16% (95% CI, 13-20), and 25% (95% CI, 20-31). Compared with no treatment, anticoagulant therapy obtained higher recanalization (RR 2.39; 95% CI, 1.66-3.44) and lower thrombosis progression (RR 0.24; 95% CI, 0.13-0.42), major bleeding (RR 0.73; 95% CI, 0.58-0.92), and overall mortality (RR 0.45; 95% CI, 0.33-0.60). These results demonstrate that anticoagulant therapy improves SVT recanalization and reduces the risk of thrombosis progression without increasing major bleeding. The incidence of recurrent VTE remains substantial also in anticoagulated patients. Effects were consistent across different subgroups of patients.