Objectives: To compare the cost-utility of five strategies for preventing esophageal variceal bleeding: (1) universal primary beta-blocker prophylaxis; (2) selective primary beta-blocker prophylaxis; (3) primary endoscopic rubber band ligation (EBL) prophylaxis; (4) secondary beta-blocker prophylaxis; and (5) secondary EBL prophylaxis. The economic viewpoint was that of third-party payers. Methods: A decision analysis was performed based on a six-state Markov model. Data on the transition probabilities between states for each prophylactic strategy were derived from a systematic search of the literature. Data on the cost of each strategy were from hospital charges to patients with bleeding esophagogastric varices admitted to the authors? hospital during the years 2002 to 2004. Effectiveness was measured using Quality Adjusted Life-Years (QALY). The outcome of the analysis was the incremental cost-utility ratio between the two most effective strategies. The cost-utility ratios were compared with the willingness-to-pay of Baht 10,000 (250 US dollars) or Baht 100,000 (2500 US dollars). Both one-way and multiway sensitivity analyses were performed. Results: Primary EBL prophylaxis was the most cost-effective long-term (greater than five years) strategy for the prevention of bleeding esophageal varices, while universal primary beta-blocker prophylaxis was most cost-effective in the short term. Sensitivity analyses did not substantially affect this result. Conclusion: Primary EBL prophylaxis is the recommended strategy for the prevention of esophageal varices bleeding in the long-term.