Objective: Portal vein thrombosis (PVT) is a rare and severe clinical manifestation of antiphospholipid syndrome (APS), as well as a predictor of poor prognosis. This study was conducted to explore the clinical features and risk factors of PVT in APS patients. Methods: A total of 123 APS patients diagnosed from 2012 to 2019 were retrospectively enrolled. The diagnosis of PVT was made according to the 2009 American College of Liver Diseases (AASLD) criteria. Clinical and laboratory data were collected. A multivariate (MV) logistic regression model was constructed using a stepwise forward selection procedure among those candidate univariables with P values<0.10. Results: A total of 28 cases with PVT, and 95 control cases without PVT were finally enrolled.The 28 APS-PVT patients included 5 males and 23 females with age range from 17 to 63 years. Clinical manifestations included acute thrombosis in 8 patients, chronic thrombosis in 16, and 4 with portal vein spongiform. As to the involved vessels, single portal vein thrombosis was seen in 20 patients, portal combined with superior mesenteric vein (SMV) and splenic vein in one patient, portal plus SMV in 4 and only SMV in 3 patients. Other manifestations were portal hypertension (16/28), esophageal varices (13/28), spleen infarction (7/28) and gastrointestinal bleeding (4/28). Two antiphospholipid antibodies were positive in 13 cases. Triple positive antibodies were seen in 7 cases. Multivariate logistic regression analysis showed that disease duration less than 0.5 years (OR=72.74, 95%CI 7.50-705.45, P<0.001), hypoalbuminemia (OR=356.45, 95%CI 19.19-6 620.14, P<0.001), and elevated erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) (OR=14.41, 95%CI 1.49-139.20, P<0.001) were independent risk factors for PVT in APS. Conclusion PVT is usually misdiagnosed due to insidious onset. Short disease duration, hypoalbuminemia and elevated ESR/CRP are risk factors for PVT in APS. Better understanding, early diagnosis and treatment will improve the clinical outcome.