ABSTRACTMalaria chemoprevention using mefloquine has become the WHO standard regimen for military personnel who stay in the endemic area for an extended period of time. We reported a case of Plasmodium ovale infection in a young Indonesian Soldier following one year mefloquine prophylaxis 250 mg weekly. Typical fever and chills were experienced two weeks after returning from one year duty in Congo, West-Central Africa. The diagnosis of ovale malaria was made by peripheral blood smear, and 35/250 parasites in small microscopic view was found. Then, he recovered after dihydroartemisin and primaquine combination therapy. This was an unusual case of long-term prophylaxis failure since mefloquine has been recognized as the agent for malaria prevention, even multi-drug-resistance Plasmodium. Dormant stage of Plasmodium ovale, quinoline-resistance potential, and the efficacy of mefloquine itself are discussed as the cause of that phenomenon.