OBJECTIVES: HAV is the most common cause of viral hepatitis in Latin America. We aimed to assess the cost-effectiveness of universal HAV immunization in Mexico. METHODS: A published dynamic transmission model was used to project the annual frequency of symptomatic HAV infections (sHAV) for a 25-years timeframe. A decision tree allowed estimating the health and economic burden associated with sHAV for either a one-dose or a two-dose scheme in toddlers as well as without vaccination. A 80% vaccine coverage was used by weighting the data reported for 70% and 90% scenarios. Analysis was conducted from the perspective of the public health care institutions. Direct medical costs comprising both acquisition and administration of HAV vaccine besides medical care of sHAV cases were assessed. Costs are expressed in 2012 Mexican pesos (MXN). An average disutility value of 0.019 was imputed to each sHAV case. Exhaustive sensitivity analyses were performed. RESULTS: Without vaccination 15,178,489 sHAV are expected for the period 2012-2036. Direct medical costs of $10,447 million MXN will be imposed by these cases, which will also entail a loss of 242,943 quality-adjusted life years (QALY). The one-dose scheme led to 36% and 32% reductions in the frequency of sHAV and QALY lost respectively, whereas for the two-dose scheme these reductions were of 54% and 45%. Incremental cost-utility ratios of $22,079 and $42,843 MXN were calculated for one-dose and two-dose schemes, respectively. The cost per additional QALY gained with two-dose versus one-dose scheme was $94,557 MXN. All these figures are less than the GDP per capita in Mexico ($136,384 MXN). Model was robust; one-dose and two-dose schemes were preferred in 42 and 57% of the second-order Monte-Carlo simulations. CONCLUSIONS: These results suggest that universal vaccination of toddlers against HAV in Mexico (either with a 1-dose or a 2-doses scheme) is a highly cost-effective intervention.