PURPOSE: Acute portal and splenic vein thrombosis (APSVT) after hepatobiliary and pancreatic (HBP) surgery is a rare but serious complication and a treatment strategy has not been well established. To assess the safety and efficacy of anticoagulation therapy for treating APSVT after HBP surgery. METHODS: We performed a retrospective case-control study of 82 patients who were diagnosed with APSVT within 4 weeks after HBP surgery from October 2002 to November 2012 at a single institute. We assigned patients to the anticoagulation group (n = 32) or nonanticoagulation group (n = 50) and compared patient characteristics, complications, and the recanalization rate of APSVT between these two groups. RESULTS: APSVT was diagnosed a mean of 8.6 +/- 4.8 days after HBP surgery. Patients' characteristics were not significantly different between the two groups. There were no bleeding complications related to anticoagulation therapy. The 1-year cumulative recanalization rate of anticoagulation group and nonanticoagulation group were 71.4% and 34.1%, respectively, which is statistically significant (log-rank test, P = 0.0001). In Cox regression model for multivariate analysis, independent factors associated with the recanalization rate of APSVT after HBP surgery were anticoagulation therapy (P = 0.003; hazard ration [HR], 2.364; 95% confidence interval [CI], 1.341-4.168), the absence of a vein reconstruction procedure (P = 0.027; HR, 2.557; 95% CI, 1.111-5.885), and operation type (liver resection rather than pancreatic resection; P = 0.005, HR, 2.350; 95% CI, 1.286-4.296). CONCLUSION: Anticoagulation therapy appears to be a safe and effective treatment for patients with APSVT after HBP surgery. Further prospective studies of larger patient populations are necessary to confirm our findings.