Abstract: Artequin®, a combination of Artesunate and Mefloquine has been reported to be effective against multidrug-resistant Plasmodium falciparum malaria in other countries but not in Nigeria. We have now evaluated the efficacy and safety of this drug in the treatment of malaria in a high malaria transmission area. The WHO protocol was followed and the Health Centre of the Community was used. Out-patients having amongst other criteria, a pre-treatment parasite density of ≥1000 μL-1 of blood were enrolled for the study. Informed Consent was obtained and the drugs were given on days 0, 1 and 2. Each patient was followed up to day 28. Results showed that of the 1453 patients screened, 120 met the enrolment criteria but 115 (58 adults and 57 children) completed the trial. The success rates in adults on D1, D2, D3, D7, D14 and D28 were 53.4, 94.8, 100, 100, 100 and 98.3%, respectively. The success rates in children were 22.8, 98.25, 100, 100, 100 and 93.0%, respectively. Parasite clearance times in adults and children were 36.4 and 42.9 h, respectively. The mean fever clearance times were 11.75 and 12.25 h, respectively. Artequin® exhibited marked antigametocyte activity, with a gametocyte clearance time of 51.0 h. There were no major adverse reactions. The values of haematological and clinical indices of safety were within normal ranges. We conclude that Artequin® is efficacious, safe and well tolerated. Its use in the treatment of malaria is therefore recommended.