An open randomized clinical trial study was carried out to compare efficacy and tolerability of artesunate mefloquine 25 mg/kg body weight (Artequin paediatric) versus artemether lumefantrine (Coartem) in the treatment of uncomplicated Plasmodium falciparum malaria in children. In each arm, 160 patients were assigned to receive either AS + MQ or AL with 28 days follow-up. The adequate clinical and parasitological response at Day 28 for per protocol analysis was after polymerase chain reaction correction, 100% for AS + MQ and 96.8% for AL. In the intention-to-treat analysis, the respective cure rates were 96.2% for AS + MQ and 93.7% for AL. No serious adverse events (AEs) were reported. The most frequent AE was vomiting, 30% in AS + MQ arm and 36% in AL arm. No biological significant abnormal values related to the study drug have been reported. The new pediatric artesunate mefloquine formulated in granule fixed dose combination is well adapted to children in Africa.