Malaria is one of the parasitic infectious diseases that is still a public health problem, including in Indonesia. Southwest Sumba District in NTT Province has been classified as a high endemic malaria area with dihydroartemisinin-piperaquine (DHP) as an antimalarial since 2004. One of the problems in malaria elimination has been the treatment failure due to plasmodium resistance to antimalarial drugs. This research was conducted in January-December 2019 in the North Kodi sub-district, Southwest Sumba District, NTT Province. This study used the prospective cohort design to determine the efficacy of DHP in people with uncomplicated falciparum malaria. Two hundred thirty-three patients with uncomplicated falciparum malaria were enrolled in the study. The treatment failure was 3.9% (95% CI: 1.3-10.8), categorized as 3% ETF and 0.9% LPF. Ten patients (4.3%) were still positive on day-2. The patients still positive for malaria falciparum can be found until day-21. There is no correlation between the number of parasites and body temperature on day 0 (r =-0.0352,p-value = 0.595). The PCR uncorrected on day-42 ACPR was 96.1% (95%CI: 92.8-98.2). The results confirmed that the efficacy of DHP is still in accordance with WHO criteria and can still be used as malaria therapy in Southwest Sumba Regency. This study add information on the Efficacy of DHP from another high malaria-endemic area in Indonesia. Information on the Efficacy of DHP outside Papua is limited, and the result of this study can add information to the policy on malaria treatment in Indonesia.