Treatment failure of Artemether-Lumefantrine drug in treating uncomplicated malaria is increasing in many endemic malaria countries. Tolerance, recrudescence, and resistance of plasmodium falciparum and plasmodium vivax parasites to the drug are increasing all over the world. We aimed to measure the treatment failure of antimalarial Artemether-Lumefantrine (Coartem) and it is contributing factors in uncomplicated malaria among adults in health centers. This study was a descriptive cross-sectional health-facility-based study conducted from the first of April to the end of June 2022 and included 166 malaria patients with positive test results for malaria visited health centers. 9.6% of malaria patients were not responding to coartem, 6.0% of them were plasmodium falciparum, 2.4% were plasmodium vivax, and 1.2 were mixed infections. Thirty-one percent of those not taking the drug with the fatty meal tested positive for malaria after two weeks of receiving coartem, and 25% of those not adherent to the treatment timetable have not cleared the parasite despite receiving coartem. The results showed that nearly one-third of the patients received Coartem without laboratory tests for malaria. Artemether-Lumefantrine is becoming less effective in the treatment of uncomplicated malaria among adults in Khartoum state, Sudan. Prospective studies are needed to assess the frequency of treatment failure and the contributing factors that assist in decreasing drug efficacy. We also encourage pharmacists not to give antimalarial treatment without a medical prescription and a positive test.