BACKGROUND. Nonadherence to chemoprophylaxis could explain why some travelers get malaria. Adherence is notoriously difficult to assess, and most studies have been conducted using questionnaires. This study aims at assessing continuous adherence more accurately with the help of an electronic pillbox. METHODS. Adult travelers to sub-Saharan Africa had to fill a questionnaire on demographic and travel data, drug intake, and adverse events. They received oral and written information about malaria and mefloquine prophylaxis and a Medication Event Monitoring System (MEMS, Aardex, Zug, Switzerland), ie, a bottle closed with a cap containing a microprocessor recording date and time of all openings, filled with the exact number of mefloquine 250 mg tablets (Lariam, Roche Reinach, Switzerland). The MEMS) was returned with the questionnaire after completion of chemoprophylaxis. RESULTS: According to the MEMS, only 26 of 81 travelers (32.1%) took all the doses at the expected date, another 8 (9.9%) did so but starting late with the first dose, and 19 others (23.5%) took all the pills but with intervals of +/-1 day from the right date. Another eight (9.9%) took all the pills but in a random way. The remaining 20 travelers (24.7%) missed some doses, mainly after return. Strict adherence as assessed by electronic monitoring was therefore lower than adherence measured by questionnaire (32.1% vs 48% in taking all the tablets on the right day). There was no difference between the two methods when a broader definition of adherence was applied [taking all the tablets on the right day (+/-1 day); 53/81 (65.4%)], but the MEMS showed that some answers to the questionnaire were not reliable. CONCLUSION: The use of electronic pillboxes confirms the low adherence of travelers to mefloquine chemoprophylaxis in spite of extensive information about the disease and its prevention. Electronic assessment of pill taking, for the first time applied to malaria chemoprophylaxis, gives new insights into the real adherence of travelers.