Hepatitis B immunization is recommended for all American children, and hepatitis A immunization is recommended for children who live in areas with elevated disease rates. Because hepatitis A and B occur most commonly in young adults, the authors examined the cost effectiveness of college-based vaccination. They developed epidemiologic models to consider infection risks and disease progression and then compared the cost of vaccination with economic, longevity, and quality of life benefits. Immunization of 100,000 students would prevent 1,403 acute cases of hepatitis A, 929 cases of hepatitis B, and 144 cases of chronic hepatitis B. Hepatitis B vaccination would cost the health system $7,600 per quality-adjusted life year (QALY) gained but would reduce societal costs by 6%. Hepatitis A/B vaccination would cost the health system dollar 8,500 per QALY but would reduce societal costs by 12%. Until childhood and adolescent vaccination can produce immune cohorts of young adults, college-based hepatitis immunization can reduce disease transmission in a cost-effective manner. (Contains 2 figures and 3 tables.)