Currently, Artemether-lumefantrine (ALu) is the only ACT recommended by the Ministry of Health and Social Welfare and therefore testing of new ACTs such as dihydroartemisinin-piperaquine (DHA-PQ) is important because alternative drugs are urgently required. Meanwhile, NMCP is revising the guidelines for treatment of malaria in Tanzania and DHA-PQ has been earmarked as an alternative ACT to be used together with ALu. However, efficacy and safety data of DHA-PQ is missing since no studies have been done in Tanzania. Thus, a study is proposed to assess the efficacy and safety of DHA-PQ Vs ALu and provide important data which will enable the NMCP to make informed decisions; and possibly recommend DHA-PQ in the new Malaria treatment guidelines as the second line drug for the treatment of uncomplicated malaria in the country.