Esophageal variceal hemorrhage (EVH) is a serious and expensive sequela of chronic liver disease, leading to increased utilization of resources. Today, endoscopic sclerotherapy (ES) and endoscopic ligation (EL) are the accepted, community standards of endoscopic treatment of patients with EVH. However, there are no published studies comparing the economic costs of treating EVH using these interventions. As part of a prospective, randomized trial comparing ES and EL for the treatment of EVH, we estimated the direct costs of health care utilization and cost-effectiveness for the prevention of variceal rebleeding and patient survival at 1-year follow-up. Treatment groups were similar in incidence of variceal rebleeding (41.9% vs. 42.9%), variceal obliteration (41.9% vs. 40.0%), hospital days, blood transfusions, shunt requirements, and survival (71.0% vs. 60.0%). There were significantly more treatment failures for active bleeding using EL (42% vs. 0%; P = .027) and esophageal stricture formation in the ES-treated patients (19.4% vs. 2.9%; P = 0.03). Median total direct cost outcomes were similar between groups (EL = $9,696 and ES = $13,197; P = .46). EL and ES had similar cost/variceal rebleeding prevented ($28,678 vs. $29,093) and cost/survival ($27,313 vs. $23,804). In the subgroup of active bleeders, ES had a substantially lower cost/survival ($28,523 vs. $51,696). We conclude that resource utilization was similar between treatment groups and that the choice of endoscopic therapy for EVH must still rely on clinical grounds. Further studies comparing costs and resource utilization in this patient population are needed.