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Introduction: The decrease in the efficacy of antimalarial drugs in the world and in Colombia hampers its control., Objective: The in vivo therapeutic efficacy of the amodiaquine+sulfadoxine-pyrimethamine combination was evaluated in the treatment of uncomplicated Plasmodium falciparum malaria and of chloroquine for P. vivax malaria., Materials and Methods: From May to November 2006, in vivo efficacy studies of malaria treatments were undertaken in Tierralta, Córdoba, northeastern Colombia. Standard protocols were followed as recommended by the World Health Organization/Panamerican Health Organization, with some modifications. Patients older than two years with single P. falciparum or P. vivax infection, with asexual parasitemia between 500 and 50,000 parasites/microl, were selected according to established inclusion and exclusion criteria. Supervised treatment was administered, and clinical and parasitological follow-up was carried out on days 0 (inclusion), 1, 2, 3, 7, 14, 21 and 28. The outcome was defined as adequate clinical and parasitological response, early therapeutic failure, or late therapeutic failure., Results: Of 53 subjects selected, 50 (94.3%; CI 70%-100%) presented adequate clinical and parasitological response to the amodiaquine+sulfadoxine-pyrimethamine treatment for uncomplicated falciparum malaria. One patient presented early therapeutic failure, and two developed late therapeutic failure. All of the 50 patients (95%CI: 74%-100%) in the invivo efficacy study of chloroquine for vivax malaria presented adequate clinical and parasitological response., Conclusion: In Cordoba, the amodiaquine+sulfadoxine-pyrimethamine combination and chloroquine show a high efficacy for the treatment of uncomplicated falciparum and vivax malaria, respectively.