Objective: To discuss the safety and feasibility of transjugular intrahepatic portosystemic shunt (TIPS) combined with Amplatzer plugging device therapy in treating symptomatic portal hypertension and large spleno - gastric - renal shunt in cirrhosis. Methods: A total of 28 patients with decompensated cirrhosis complicated by upper gastrointestinal bleeding or intractable ascites together with large spleno - gastric - renal shunt, who were encountered at the hospital during the period from March 2011 to June 2012, were collected. Of the 28 patients, the diameter of the spleno - gastric - renal shunt was > 1.2 cm in 9, and these 9 patients were enrolled in the study. First, the conditions of portal vein, varices, spleno - gastric - renal shunt were evaluated by indirect portography via renal vein or direct portography via hepatic vein. Then, a portosystemic shunt between intrahepatic portal vein and hepatic vein was established via a right jugular vein access. Subsequently, an Amplatzer plugging device was released. Finally, a covered stent was placed into the liver parenchyma. stent position, blood flow, varices and spleno - gastric - renal shunt were evaluated. If necessary, embolization of varices was carried out with coils. Portosystemic pressure gradient was determined. Results: Successful TIPS combined with Amplatzer plugging device procedure was accomplished in all 9 patients, and no complications occurred during operation. In 4 patients TIPS was performed with simultaneous spleno - gastric - renal shunt occlusion, and neither shunt dysfunction nor hepatic encephalopathy occurred after the treatment. In 5 patients TIPS was performed first. After the treatment, severe hepatic encephalopathy (grade III) occurred in 4, shunt dysfun-ction in 3 and upper gastrointestinal bleeding in one case. TIPS balloon dilatation followed by spleno - gastric - renal shunt occlusion was carried out in 5 patients, and after the treatment no shunt dysfunction occurred, only one patient developed mild hepatic encephalopathy (grade I). Conclusion: For the treatment of cirrhosis associated with symptomatic portal hypertension and large spleno - renal or gastric - renal shunt, transjugular intrahepatic portosystemic shunt combined with Amplatzer plugging device therapy is safe and feasible. This therapy can effectively prevent the occurrence of hepatic encephalopathy and variceal bleeding caused by cirrhotic portal hypertension with large spleno-gastric-renal shunt.