Coartem is a fixed-dose combination of artemether-lumefantrine that, given in six doses, provides effective treatment for children with uncomplicated Plasmodium falciparum infection in areas with highly endemic and multidrug-resistant malaria. In Rwanda since 2001, amodiaquine+sulfadoxine-pyrimethamine (AQ+SP) has been the first-line treatment, but resistance to this combination has rapidly emerged and spread. Coartem was considered as a possible alternative, and a randomised, open-label, clinical trial to test its safety, tolerability and efficacy was carried out in 2004-2005. Five hundred children aged 12-59 months with uncomplicated P. falciparum malaria were randomly allocated to AQ+SP or Coartem. Patients were followed up until day 28 after treatment. Adverse events and clinical and parasitological outcomes were recorded. Adequate clinical and parasitological response (ACPR) was significantly higher in children treated with Coartem than in those treated with AQ+SP: the PCR-adjusted 28-day ACPR was 96.68% for Coartem and 79.35% for AQ+SP. Both treatments rapidly cleared parasitaemia and fever, although parasite clearance was significantly faster in children treated with Coartem. Mean packed cell volume increased in all patients, with no significant differences between treatments. Coartem proved to be more efficacious than AQ+SP, with a good safety and tolerability profile.