Although both beta-blockade (BB) and endoscopic variceal ligation (EVL) are used for primary prevention of variceal bleeding (VB) in patients with cirrhosis with moderate to large esophageal varices (Ells), the more cost-effective option is uncertain. We created a Markov decision model to compare BB and EVIL in such patients, examining both cost-effectiveness (cost per life year [LY]) and cost-utility (cost per quality-adjusted life year [QALY]). Outcomes included cost per LY, cost per QALY, proportions of persons with VB, TIPS, and all-cause mortality. EVL and BB were compared using the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). When considering only LYs, initial EVIL exceeds the benchmark of $50,000/LY, with an ICER of $98,407. However, when quality of life (QoL) is considered, EVL is cost-effective compared to BB (ICUR of $25,548/QALY). In sensitivity analysis, EVL is cost-effective if the yearly risk of EV bleeding is >= 0.26 (base case 0.15), the relative risk of bleeding on BB is >= 0.69 (base case 0.58), or if the relative risk of bleeding with EVL is < 0.27 (base case 0.35). The ICUR favored EVL unless the relative risk of bleeding on BB is < 0.46, the relative risk of bleeding with EVL is > 0.46, or the time horizon is :5 24 months. Whether EVL is "cost-effective" relative to BB therapy for primary prevention of EV bleeding depends on whether LYs or QALYs are considered. If only LYs are considered, then EVL is not cost-effective compared to BB therapy; however, if QoL is considered, then EVL is cost-effective.