Artemether-lumefantrine, a tablet formulation of these respective antimalarial compounds, has been developed for the treatment of patients with drug-resistant malaria worldwide. Many studies have shown that it is most effective of the antimalarial compounds in shortening the fever and parasite clearance times. However, several treatment failures have been reported. These failures are believed to be a consequence of poor bioavailability of the lumefantrine component when ingested without fatty food. This paper reports the first case of such treatment failure of imported malaria in Japan in a 58-year-old Japanese man who showed recrudescence of Plasmodium falciparum after treatment with artemether-lumefantrine. The drug was administered to the patient in 6 doses, each time without fatty food and on a seemingly empty stomach. It is believed that treatment failure was due to poor absorption and a subsequent low plasma concentration of lumefantrine. Although artemether-lumefantrine has not been approved for use in Japan and is thus not commonly used there at present, it is thought to be the most promising drug of choice for the treatment of drug-resistant malaria. Taking an appropriate dosage and providing patients with proper instructions on taking the drug concurrently with fatty food are required for effective treatment with artemether-lumefantrine.