Artemether-lumefantrine (AL), the ACT of first choice for the treatment of malaria in Nigeria though efficacious and well tolerated has a 6-dose regimen over three days and requires co-administration with a fatty meal for optimal absorption and efficacy. This may lead to poor compliance and consequent loss of efficacy over time. Dihydroartemisinin-piperaquine (DP) is another ACT with high efficacy and good tolerability available in Nigeria with a more user-friendly dosing regimen. In an open label randomized clinical trial, we compared the safety and efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) among 110 children aged 6 – 120 months with symptomatic acute uncomplicated malaria in Ilorin north-central Nigeria. Enrolees were followed up for 28days.107 of 110 (97.3%) enrolees completed the study. The mean age of enrolees was 71.95 ±33.25 months (range 7-120) and 47.2% (51/110) were males. Geometric mean parasite density among children who received AL was 19,158/μL (range 1,200 -197,333) and 21,908/μL (range 1024 - 186,182) for those treated with DP (ρ=0.718). Parasite clearance time for AL treated children was significantly shorter than among those treated with DP (2.35 ± 0.71 days versus 2.71±0.61 days) respectively (ρ=0.001). Fever clearance time was also significantly shorter among children who received AL (1.86 ± 0.61 versus 2.17 ± 0.43 respectively (ρ=0.005). Crude D28 cure rate was 100% among both treatment groups. AL and DP were well tolerated. AL and DP were safe and efficacious in the treatment of acute uncomplicated malaria in children from north-central Nigeria.