OBJECTIVES: To analyze the Brazilian Budget Impact Analysis (BIA) guideline and to propose a specific guideline for conducting BIA of vaccines to support national decision-making process. METHODS:: We systematically reviewed domestic and international BIA guidelines, and published BIA of vaccines to identify and discuss specific methodological issues of vaccines that are still the subject of debate in the scientific community. We critically reviewed each analytic framework element in order to propose the vaccine BIA guideline. To complement the vaccine BIA guideline, a cost calculator model was developed using Microsoft Excel to increase the standardization of the process and quality reporting. We used the example of the hepatitis A vaccine to illustrate the use of the cost calculator. RESULTS:: Ten BIA guidelines and 22 BIA of vaccines were reviewed. Literature showed no BIA guideline specific for vaccines. Most guidelines were developed for therapeutic drugs or medical devices. Vaccines and vaccination programs have different features from these technologies. Vaccines are administered to a large number of healthy persons, usually based on age or risk; they may cause adverse events in vaccinees and may benefit the entire population (vaccinated and non-vaccinated) due to reduction of the pathogen transmission (indirect effects or herd protection). The following methodological issues deserve special attention: size of eligible population, vaccine coverage, herd protection, time horizon, model choice, and cost categories (e.g. program implementation, campaigns). CONCLUSION: In order to help decision-makers formulate appropriate recommendations, these methodological issues need to be adequately addressed when vaccines are assessed.