Currently, monitoring hepatic venous pressure gradient (HVPG) have been proved to be the best predictor for the risk of variceal bleeding. We performed the study to evaluate the effect of endoscopic therapy + β-blocker vs. covered transjugular intrahepatic portosystemic shunt (TIPS) for the prevention of variceal rebleeding in cirrhotic patients with HVPG ≥16 mmHg. Consecutive cirrhotic patients with HVPG ≥16 mmHg treated with endoscopic therapy + β-blocker or covered TIPS for variceal bleeding were retrospectively gathered between April 2013 and December 2018. The variceal rebleeding rate, survival, and incidence of overt hepatic encephalopathy (OHE) were compared. A total of 83 patients were analyzed, of which 46 received endoscopic therapy + β-blocker and 37 covered TIPS. During a median follow-up of 12.0 months, the rebleeding rate (32.6 vs. 10.8%, P = 0.017) and rate of OHE (2.2 vs. 27.0%, P = 0.001) showed significant differences between the two groups, while liver transplantation-free survival (93.5 vs. 94.6%, P = 0.801) was similar. Preoperative and postoperative Child-Turcotte-Pugh scores were similar in either group. In addition, no significant differences of rebleeding rate (25.0 vs. 21.3%, P = 0.484) and survival (97.2 vs. 91.5%, P = 0.282) were observed between patients with 16 mmHg ≤ HVPG < 20 mmHg and HVPG ≥ 20 mmHg. Covered TIPS was more effective than endoscopic therapy + β-blocker in preventing rebleeding in patients with HVPG ≥16 mmHg but did not improve survival. TIPS also induce more OHE.