 Methods: An antimalarial drug efficacy trial will be conducted in Malawi. The participants will be febrile people 6-59 months old with confirmed uncomplicated P. falciparum infection. Patients will be sequentially allocated to receive treatment with either the dispersible formulation of artemether-lumefantrine at a dose of 212 mgkg body weight of artemether and lumefantrine, respectively, per dose, given twice a day for 3 days; or co-formulated artesunate-amodiaquine at a dose of 4 mgkgday artesunate and 10 mgkgday amodiaquine once a day for 3 days; or co-formulated dihydroartemisinin-piperaquine at a dose of 4 mgkgday dihydroartemisinin and 18 mgkgday piperaquine once a day for 3 days. Clinical and parasitological parameters will be monitored over a 42-day follow-up period to evaluate drug efficacy. The study will be conducted from January to December, 2011. The results of this study will be used to assist the Ministry of Health in Malawi in assessing the current national treatment guidelines for uncomplicated P. falciparum malaria. 