Purpose: To compare current primary prevention options using a decision analytic model that projects health and economic outcomes. Methods: A Markov model was developed for three strategies which included beta-blockers, esophageal variceal ligation, and no intervention. The model included the relevent clinical outcomes related to cirrhosis with HCV (esophageal variceal bleeding, esophageal variceal rebleeding, hepatic decompensation, hepatocellular carcinoma, liver transplant, and death). We performed a systematic review of MEDLINE and EMBASE to identify cohort studies describing the natural history of cirrhotics with HCV; randomized clinical trials comparing beta-blocker versus placebo or variceal band ligation in preventing the first variceal bleed among cirrhotics with grade 2 or 3 esophageal varices; randomized clinical trials in terms of the benefits of beta-blocker on cardiovascular diseases that is associated with around 20% patients with cirrhosis; and utility studies characterizing the utility of the health states related to cirrhosis. We used a weighted logistic regression model to project the transition probabilities between the health states and the occurence of the first bleeding episode. The annual health care cost related to each health states was estimated by the adjusted cost from the Toronto Western Hospital,. RESULTS: Primary prevention with beta-blockers was associated with a longer life expectancy than variceal ligation (11.06 life years vs. 10.19 life years), and was less costly. Beta-blocker therapy was also associated with a greater quality adjusted life expectancy (8.33 QALYs vs. 8.14 QALYs). Sensitivity analysis was conducted in terms of the occurence of the first bleed, death related to bleed, the methods for measuring health state utility, and the adjusted health care cost in managing cirrhosis. Variations in these parameters within the range of clinical plausibility demonstrated that beta-blocker at least had the equivalent QALYs with variceal band ligation but less cost. The beta-blocker strategy remained dominant. Conclusions: Our decision analytic model suggests that non-selective beta-blocker therapy is associated with less cost but not less benefits than variceal band ligation in preventing the first esophageal variceal bleed among cirrhotics with HCV and grade 2 to 3 varcies.