OBJECTIVES: To estimate the cost-effectiveness of rabies vaccination program in dogs to prevent human rabies in Colombia. METHODS: A Markov model with daily cycles was designed to simulate the dynamics of the transmission of rabies in the dog population of Colombia. A Literature review for identifying transmission parameters within dog population and transmission to humans was carried out. The model considered two alternatives: No vaccination and dog vaccination (comparing different vaccination coverage). The burden of disease in human population, during one year, in terms of years of life lost (YLL) was estimate and program and care costs were collected from a third payer perspective. Incremental cost effectiveness ratio (ICER) of vaccination versus no vaccination was estimated. All cost were adjusted to 2013 US dollars. RESULTS: With no vaccination 58,591 of dog rabies cases were estimated whit 5 human cases and 338 YLL. With vaccination at a 68% coverage and 75% of vaccine effectiveness, 28,664 dog cases and 2 human cases were estimated. The vaccination costs were US $ 777,331.76; administration costs of US $ 1,426,463.00 and wastage costs were estimated at US $ 77,733.18; for a total program cost of US $ 220,379,48. The variation in vaccination coverage, introduced significant changes, the most significant change is reflected in the costs to present a case of human rabies; with the current coverage is US $ 10,394.87 to $ 6,933.36 USD (90% coverage). The incremental cost effectiveness ratio (ICER) would be between 654 and 704 per additional year of life gained.  CONCLUSIONS: Increase vaccination coverage in dogs to decrease the incidence of human rabies is a cost-effective strategy in Colombia.