The objective of this study was to determine the cost-effectiveness of zinc supplementation for the treatment of acute diarrhea (AD) in children younger than 5 years in Colombia.The cost-effectiveness analysis was performed from the perspective of the Colombian health system. The standard treatment with the addition of zinc was compared with the standard treatment without zinc in children younger than 5 years. The time horizon was 1 month. Effectiveness was extracted from a systematic review of literature. The specific data for Colombia were taken from local databases and observational studies. To determine the costs, a typical case was constructed by reviewing guidelines and medical records and validated by experts. To evaluate the resources consumed, Colombian tariff manuals were used. Costs were stated in Colombian pesos (COP) and US dollar (USD) for 2010. Deterministic sensitivity analysis was performed to evaluate the impact of changes in cost and effectiveness of the strategies on the results from the model.The results from the model indicate that zinc supplementation is a dominant strategy; it is less costly and more effective than standard treatment without zinc (reduction of $15,210 COP [8.14 USD] per child). The results are sensitive to changes in the probability of hospitalization and of persistent diarrhea.Zinc for the treatment of AD is a highly cost-effective strategy and is recommended for inclusion in the benefit plan of the Colombian health system. This intervention is more cost-effective in children with a higher risk of persistent diarrhea and hospitalization.