. Malaria is one of the leading causes of mortality in risk populations such as infants, children, and pregnant women. Moreover, antimalarial drugs resistance, particularly Plasmodium falciparum malaria, has become a major problem in malaria control. South-East Sulawesi is a malaria endemic area where about 28,205 and 32,040 cases of malaria were reported in 2010 and 2011, respectively. Artesunate-amodiaquine combination therapy (AAQ) has been used since 2004 as first-line treatment for uncomplicated P. falciparum malaria in South-East Sulawesi. Therefore, monitoring its therapeutic efficacy is essential to stopping the spread of ACT resistance. To monitor the therapeutic efficacy of AAQ in South-East Sulawesi, a single-arm prospective study was conducted. Subjects, who received AAQ, were followed-up for 28 days. The results showed that the proportion of clinical and parasitological cure on day-28 without recrudescence was 100%. Moreover, no parasites were found on day-3 of follow-up.