Objective: To evaluate the efficacy of high mesocaval shunt (HMCS) plus portal-azygous disconnection for treatment of portal hypertension. Methods: The clinical date of 144 patients with portal hypertension undergoing HMCS plus portal-azygous disconnection in our hospital from 2001 to 2011 were retrospectively analyzed. Results: Of the patients, 89 cases were male and 55 cases were female, whose ages ranged from 19 to 55 years. There were 119 cases of posthepatitic cirrhosis and 25 cases cirrhosis secondary to other causes. All the patients had moderate or severe esophageal and gastric fundal varices, and 128 cases had the history of bleeding more than once. Eighty-six cases were Child′s grade A and 58 cases were Child′s grade B in terms of liver function grades before operation. All the patients underwent HMCS plus portal-azygous disconnection. The free portal pressure of the patients decreased 9 cm H2O in average, and their white blood cells and platelet count significantly increased or returned to normal after surgery. The postoperative complications comprised four cases of wound infection, one case of intra-abdominal infection, 12 cases of fever, two cases of hepatic encephalopathy, 1 case of graft thrombosis and 14 cases of chylous leakage. All the complications mentioned above were resolved by non-surgical therapy. Only 1 patient died of hepatorenal syndrome. One hundred and six patients were followed up for 6 months to 10 years, of whom the subjective symptoms were obviously improved in 95 cases after surgery and they had no gastrointestinal rebleeding, hepatic encephalopathy, ascites or other symptoms, the total effective rate was 89.6% (95/106). Hepatic encephalopathy occurred in four cases and graft thrombosis in three cases, which were all resolved by non-surgical treatment. Upper gastrointestinal rebleeding occurred in four cases, of whom three cases died, and 1 patient was cured by non-surgical treatment. Conclusions: High mesocaval shunt plus portal-azygous disconnection is an effective treatment for portal hypertension, it with low complication incidence and better short as well as long term results.