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We report a case of a patient returning from Cameroon who developed Plasmodium ovale malaria, despite atovaquone/proguanil (AP, Malarone) prophylaxis, which is widely used for the prevention of chloroquine-resistant malaria. AP is indeed active only on schizont blood forms of P. ovale but not against liver-stage hypnozoites and does not realize effective prophylaxis against delayed onset of P. ovale malaria. Hence, this case illustrates the risk of failure with Malarone for the prophylaxis of P. ovale infection for travelers in endemic regions. Travelers returned from risk areas with symptoms suggestive of malaria, should not have the diagnosis of P. ovale (or P. vivax) infection discounted, despite a history of compliance with a standard chemoprophylactic regimen.