Plasmodium falciparum isolates were collected from 29 malaria patients treated with artemether-lumefantrine in Mayotte in 2013-2014. Twenty-four cases (83%) consisted of imported malaria. Seventeen percent of the isolates presented mutations in one of the six K13-propeller blades (N490H, F495L, N554H/K and E596G). A total of 23.8% of the isolates from the Union of Comoros showed K13-propeller polymorphisms. Three of the 18 isolates (16.7%) from the Grande Comore showed polymorphism (N490H, N554K and E596G).