The management of severe malaria is a major challenge in the health care services in sub-Saharan Africa. This study aimed to assess the efficacy and safety of artemether and quinine in severe malaria at Complexe pédiatrique of Bangui, Central African Republic. A total of 212 children among 1125 hospital admissions (18.8%), and aged 6 to 59 months were randomly treated with artemether and quinine. Anemia (58.5%) and seizures (33.5%) were the major syndromes observed. On the third day of follow up, a regression of clinical signs and parasite clearance were observed in 98.1% of children treated with artemether and 97.1% of children treated with quinine. The death rate was 2.3% due to anemic and neurological forms. These findings show that the artemether and quinine have similar efficacy. Hence, associated with adequate intensive health care, the use of these antimalarial drugs can significantly reduce mortality from severe malaria in the Central African Republic.