Abstract Introduction: The study was conducted to evaluate therapeutic efficacy of Coartem® for the treatment of uncomplicated falciparum malaria in Wondogenet Woreda, Sidama Zone, Ethiopia. Since the spread of Plasmodium falciparum, parasite resistance to almost all antimalarial monotherapies is a serious impediment to malaria control. Artemether-lumefantrine (Coartem®) therapy has been in use as the first-line treatment for uncomplicated falciparum malaria since 2004 in Ethiopia. Methods: The study was designed according to WHO study protocol. The study outcomes were classified into Early Treatment Failure (ETF), Late Clinical Failure (LCF), Late Parasitological Failure (LPF) and Adequate Clinical and Parasitological Response (ACPR). Results: Primary study was conducted on ninety-nine P. falciparum mono-infected consenting patients who were enrolled in the 28-day in vivo Coartem® treatment followup study. Based on this, the overall cure rate for Coartem® was 98.9% (PCR uncorrected).