Background Some studies have shown that transjugular intrahepatic portosystemic shunt (TIPS) placement within 72 hours of admission improves survival in patients at high risk who present with acute variceal bleeding. However, the role of small-diameter covered TIPS in the secondary prophylaxis of variceal bleeding is still debatable. Purpose To compare the efficacy of 8-mm TIPS and endoscopic variceal ligation (EVL) plus propranolol in the prevention of variceal rebleeding among participants with advanced cirrhosis. Materials and Methods Between June 2015 and December 2018, participants admitted to the hospital for variceal bleeding were considered for enrollment in this randomized controlled trial (ClinicalTrials.gov). Participants with Child-Pugh class B or C cirrhosis were randomly assigned to receive an 8-mm covered TIPS or EVL and propranolol. The primary end point was recurrent variceal bleeding assessed using Kaplan-Meier curve analysis. Secondary end points included survival and overt hepatic encephalopathy (HE) assessed using Kaplan-Meier curve analysis. Results A total of 100 participants were enrolled, with 50 randomly assigned to the EVL plus propranolol group (median age, 54 years; IQR, 45-60 years; 29 male, 21 female) and 50 randomly assigned to the TIPS group (median age, 49 years; IQR, 43-56 years; 32 male, 18 female). The median follow-up period was 43.4 months. In the TIPS group, variceal rebleeding risk was reduced compared with variceal rebleeding risk in the EVL plus propranolol group (hazard ratio [HR], 0.31; 95% CI: 0.14, 0.69; P = .008), but the incidence of overt HE was higher in the TIPS group (30.0% vs 16.0%, P = .03). No differences in survival were observed between the two groups (1-year survival: TIPS, 98.0%; EVL plus propranolol, 92.0%; 3-year survival: TIPS, 94.0%; EVL plus propranolol, 85.7%; HR, 0.52; 95% CI: 0.19, 1.42; P = .22). Conclusion When compared with EVL plus propranolol, 8-mm TIPS led to reduced variceal rebleeding but did not impact overall survival in participants with Child-Pugh class B or C cirrhosis. Clinical trial registration no. NCT02477384 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Barth in this issue.