Chikungunya virus (CHIKV) emerged in Indian Ocean islands in 2005 and is causing an ongoing outbreak that involves >260,000 patients, including travelers returning home from these islands. We investigated cases in 4 patients returning from Mayotte and Reunion Islands with CHIKV infection and a nurse infected in metropolitan France after direct contact with the blood of a traveler. Four patients had tenosynovitis and pain at wrist pressure, and 1 had life-threatening manifestations. Four CHIKV strains were isolated, including 1 from the patient with the autochthonous case. The complete genomic sequence identified a new CHIKV variant emerging from the East/ central African evolutionary lineage. Aedes albopictus, the implicated vector of CHIKV in Indian Ocean islands, has dispersed worldwide in recent decades. High viral loads in patients returning from Indian Ocean islands to countries where Ae. albopictus is prevalent may be a source of epidemics.