A 20 year-old healthy female volunteer participated in a clinical Phase I and IIa safety and efficacy trial with candidate malaria vaccine PfLSA-3-rec adjuvanted with aluminium hydroxide. Eleven weeks after the third and last immunization she was experimentally infected by bites of Plasmodium falciparum-infected mosquitoes. When the thick blood smear became positive, at day 11, she was treated with artemether/lumefantrine according to protocol. On day 16 post-infection i.e. two days after completion of treatment, she woke up with retrosternal chest pain. She was diagnosed as acute coronary syndrome and treated accordingly. She recovered quickly and her follow-up was uneventful. Whether the event was related to the study procedures such as the preceding vaccinations, malaria infection or antimalarial drugs remains elusive. However, the relation in time with the experimental malaria infection and apparent absence of an underlying condition makes the infection the most probable trigger. This is in striking contrast, however, with the millions of malaria cases each year and the fact that such complication has never been reported in the literature. The rare occurrence of cardiac events with any of the preceding study procedures may even support a coincidental finding. Apart from acute coronary syndrome, myocarditis can be considered as a final diagnosis, but the true nature and patho-physiological explanation of the event remain unclear.