Although mefloquine is the only drug licensed for malaria chemoprophylaxis in Japan, there have been few reports describing the effects of and adverse events in the prophylactic usage of mefloquine in a Japanese population. We therefore performed a questionnaire-based study in 21 travelers who were prescribed mefloquine for malaria chemoprophylaxis between October 2001 and December 2003. The study revealed that only 8 out of 21 (38.1%) of the travelers could complete the prophylaxis schedules. Another 8 travelers (38.1%) with incomplete adherence stated that they did not take mefloquine because of either actually experienced or anticipated adverse events. Twelve of the 16 travelers (75.0%) who took mefloquine complained of at least one adverse event probably related to mefloquine. As an overall impression about mefloquine chemoprophylaxis, 14 of the 21 travelers stated that they would take mefloquine again for the next travel to malaria-endemic areas, although 5 of them were concerned about adverse events. These results suggest that, although mefloquine is an indispensable drug for malaria prevention, other effective and well-tolerated chemoprophylactic antimalarials should be available for Japanese travelers who do not tolerate mefloquine.