OBJECTIVES: Respiratory syncytial virus (RSV) remains one of the major reasons of re-hospitalization among children with congenital heart disease (CHD). This study estimated the cost-effectiveness of palivizumab prophylaxis versus placebo, in Mexico, from the societal perspective. METHODS: A decision-analytic model combining a decision tree structure in the first year and a Markov structure in later years was constructed to evaluate the benefits and costs associated with palivizumab prophylaxis among children with CHD. In the first year of the model, children were at risk of mild (i.e. medically attended) and severe (hospitalized) disease due to RSV infection. The risk of delayed and complicated heart surgery due to severe disease due to infection was also accounted for. In later years, patients were at risk of developing asthma and allergic sensitization as sequelae of RSV infection. Input data for the model were derived from the pivotal clinical trial and systematic literature reviews. Indirect costs included parental absence from work, travel costs, and RSV nosocomial infections. In the base case analyses, costs and effects were discounted at 5%. Results discounted at 0% and 3% are presented as scenario analyses. RESULTS: Over a lifetime horizon palivizumab prophylaxis yielded additional quality-adjusted life years (QALYs) at additional costs. In the base case analysis, incremental costs and QALYs were estimated to be $2,864 and 0.09, respectively, resulting in an ICER of $33,762/QALY gained. The corresponding figures in the analysis with 0% discount rates were $2,641, 0.22, and $11,834/QALY gained, respectively, whereas in the analysis with 3% discount rates these were $2,786, 0.11, and $24,765/QALY gained, respectively. CONCLUSIONS: The model demonstrated that palivizumab prophylaxis is a cost-effective preventive strategy for children with CHD in Mexico. High discount rates penalize preventive treatments for which health gains occur only in the future. Thus the use of lower discount rates may be more appropriate.