Background: The number of tourists visiting malaria endemic regions is continuously increasing. The risk of aquiring malaria infection can largely be prevented by the regular use of chemoprophylactic drugs combined with using protective measures against mosquito bites. In a prospective study we wished to determine the tolerability of chemoprophylactic drugs and the factors that influence compliance with malaria chemoprophylaxis and antimosquito measures. Method: German travelers (n = 6504) who attended the Berlin Institute of Tropical Medicine in Berlin for pretravel medical advice were interviewed by phone 4 weeks after their journeys about compliance with the recommended malaria chemoprophylaxis and the incidence of side effects. Results: Compliance was better with mefloquine (94.5%) than with chloroquine (85.9%) (p<.001) or chloroquine plus proguanil (79.8%) (p<.001). Compliance was influenced by the purpose of travel, duration of stay, places of stay, and adverse reactions. Side effects occurred in 20.6% of the travelers who took chemoprophylactic drugs. There was no significant difference in the incidence of side effects between the three drug regimens, but people who took mefloquine more often reported neuropsychiatric reactions (6.5% versus 3.9% with chloroquine and 3.6% with chloroquine and proguanil; p<.001)). Side effects were usually mild to moderate and in no instance required hospitalization. People who took their drugs with meals less often reported side effects (15.2%) (p<.01). Conclusion: The knowledge of user profiles (and particular factors that presage side effects and noncompliance) may help us to improve pretravel counseling, thereby reducing the risk that travelers may acquire malaria infection.