Although hepatitis A and B vaccinations are recommended for patients with chronic hepatitis C virus (HCV), the ideal vaccination strategy is not determined. OBJECTIVE: To model the cost-effectiveness of two strategies of vaccinating patients with HCV infection against hepatitis A (HAV) and hepatitis B (HBV) viruses. The strategies evaluated were: universal vaccination with the combined HAV and HBV vaccine, and selective vaccination based on immunity by blood testing. METHODS: A decision tree computer model was constructed to compare the cost-effectiveness of the two vaccination strategies from the New Mexico Veterans Affairs Health Care System (NMHAHCS) perspective. A retrospective review of all HCV patients (2542 subjects) at the NMVAHCS was performed to extract prevalence of immunity to HAV and HBV, and prevalence of decompensated liver disease. Literature review was performed to obtain other probabilities for the model. The effectiveness measure was the number of patients immune to both HAV and HBV. RESULTS: The selective strategy was less costly but less effective with a cost-effectiveness ratio of $105 per patient immune to HAV& HBV. The universal strategy was more effective but more expensive with a cost-effectiveness ratio of $112 per patient immune to HAV& HBV. Compared with the selective strategy, universal strategy was associated with an incremental cost-effectiveness (ICE) ratio of $154 per additional patient immune to HAV and HBV. The universal strategy would become more cost-effective if the cost of combined vaccine reduces by >9.7% to