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Introduction Patients with cirrhosis and portal hypertension are at high risk of oesophageal variceal bleeding. Non-selective beta-blockers (NSBBs) are standard prophylaxis, with endoscopic variceal ligation (EVL) used when NSBBs are not tolerated. 1 However, their comparative effectiveness and the value of combination therapy remain uncertain. Our meta-analysis evaluates the risks and benefits of NSBBs and EVL for primary prevention.Methods We systematically searched eight online databases for studies published to July 2025. Randomised Clinical trials (RCTs) and observational studies comparing (NSBBs) and (EVL), alone or combined, for primary prevention of oesophageal variceal bleeding in adults with chronic liver disease were included. Primary outcomes were variceal bleeding and all-cause mortality. Secondary outcomes included bleeding-related death, time to death, and liver-related complications. Random-effects models estimated risk ratios (RR) with 95% confidence intervals (CI) and standarized mean difference (SMD).Results Our network meta-analysis included 27 (RCTs) and 8 observational studies, including 5,076 patients. Interventions evaluated included EVL (n=1,976), propranolol (n=1,243), carvedilol (n=776), nadolol (n=120), and NSBBs ( n=259). Combination strategies involved EVL with propranolol (n=452), carvedilol (n=110), nadolol (n=70), or NSBBs (n=70). EVL was superior to propranolol monotherapy for preventing variceal bleeding (14 RCTs; RR 1.90, 95% CI 1.23–2.93; p=0.0036) and variceal bleeding–related mortality (12 RCTs; RR 2.03, 95% CI 1.04–3.96; P=0.0379) ( figure 1a,b). Nadolol showed no significant benefit (RR 1.80, 95% CI 0.52–6.23; p=0.3532). EVL combined with carvedilol significantly reduced all-cause mortality compared with EVL alone (23 RCTs; RR 0.40, 95% CI 0.18–0.91; p=0.0296) and prolonged time to death (2 RCTs ; SMD 0.30, 95% CI 0.04–0.57; p=0.0256). In contrast, propranolol monotherapy was associated with shorter time to death (SMD −0.86, 95% CI −1.59 to −0.12; p=0.0226) and higher risk of acute kidney injury (2 RCTs; RR 2.10, 95% CI 1.06–4.17; p=0.0341). Other secondary outcomes were not significant between interventions.Conclusions EVL is more effective than propranolol alone for preventing variceal bleeding and related mortality. Combining EVL with carvedilol offers the greatest survival benefit. In contrast, propranolol monotherapy is linked to higher bleeding risk, acute kidney injury, and earlier death.Reference EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406–60. doi: 10.1016/j.jhep.2018.03.024Abstract P61 Figure 1a)network plots for oesophageal variceal bleeding across the study population; b) treatment effects of EVL and beta-blocker on preventing variceal bleeding