Introduction: Zinc deficiency is common in children among populations in developing areas. Zinc deficiency alters the immune system and the resistance to infections.Objective: To evaluate the effect of two zinc compounds in the prevention of acute respiratory infection and acute diarrhea.Materials and methods: Randomized triple-blind community trial with 301 children between 2-5 years of age from six child daycare centers in Medellin, Colombia. Children were distributed in three groups receiving zinc amino acid chelate, zinc sulfate and placebo five days a week for 16 weeks. Daily symptoms of respiratory infection, acute diarrhea and side effects were evaluated.Results: The incidence of respiratory infection was lower with zinc amino acid chelate (1.42 per 1,000 child-days) compared with placebo (3.3 per 1,000 child-days) (RR=0.43, 95% CI: 0.196 to 0.950, p=0.049) and with zinc sulfate (1.57 per 1,000 child-days) (RR=0.90, 95% CI 0.382 to 2.153, p=0.999). The incidence of acute diarrhea with zinc amino acid chelate (0.15 per 1,000 child-days) was lower than with placebo (0.49 per 1,000 child-days) (RR=0.32, 95% CI 0.006 to 3.990, p=0.346) and with zinc sulfate (0.78 per 1,000 child-days) (RR=0.20, 95% CI: 0.0043 to 1.662, p=0.361).Conclusions: Zinc amino acid chelate had a better effect in reducing the incidence of acute respiratory infection and acute diarrhea in preschool children when compared with the other groups.Identifier in clinicaltrials.gov: NCT01791608