Although Mefloquine is commonly used as a prophylactic drug for travelers to malaria endemic areas, there are only limited reports about its adverse effects in Japanese travelers. We carried out a prospective observation study of 107 travelers who were prescribed mefloquine as chemoprophylaxis against malaria prior to their departure from November 2004 to October 2006. We carefully sought the appropriate prescription for each client according to the guidelines for Japanese overseas travelers. The clients consisted of 71 men and 36 women of whom we were able to follow 65 travelers until the end of their prophylactic procedure. Of the 65, 47 travelers completed their full course of chemoprophylaxis. Different adverse effects were reported in 19 travelers of them such as fatigue (n=9), dizziness (n=6), headache (n=3), nausea (n=3), drowsiness (n=2), strange dreams (n=2), anxiety (n=2), fever (n=1) and skin rash (n=1). Three travelers were incapable of continuing chemoprophylaxis due to the adverse effects, but no serious events were noted. Through our study, mefloquine chemoprophylaxis seemed tolerable for Japanese travelers. We believe that our detailed consultation and careful monitoring reduced the incidence of severe adverse effects and maintained the high rate of adherence to chemoprophylaxis.