BACKGROUND: Concerns have been expressed that in travelers the efficacy of the live oral Ty21a typhoid vaccine Vivotif could be lower than reported, maybe due to a lack of compliance. The purpose of this study was to examine the level of compliance with the recommendations regarding dosing, timing of dosing with respect to food intake, and storage. METHODS: Travelers were randomized into two groups: one received oral information only, and the second, a combination of oral and written information. Four criteria of compliance were applied to travelers: 3 capsules needed to be swallowed (criterion 1) on day 1, 3 and 5 (criterion 2), at least 1 hour before or 2 hours after a meal (criterion 3) and the vaccine had to be kept refrigerated (2-8 degrees C) (criterion 4). Compliance was evaluated using three different methods: a questionnaire, pill counting, and electronic monitoring using the Medication Event Monitoring System (MEMS). Storage conditions were checked by temperature tags, and viability of the vaccine was assessed by culturing the content of remaining capsules. RESULTS: The data of 115 travelers were analyzed. All the travelers took the 3 capsules. Compliance to all four criteria was complete in 68% of travelers according to the questionnaire, and 53% according to the MEMS (p =.05). Sixty-seven percent of all the doses intervals were of 48 hours +/- 6 hours, 12% being shorter than 36 hours and 7% longer than 60 hours. Eighty-seven travelers (76%) took their capsules on each alternate day. The method of information had no significant impact on compliance. Forty-two percent of tags showed exposure to temperature over 10 degrees C for more than 24 hours. Yet, no difference could be found in the viability of the vaccine compared with controls. CONCLUSIONS: Most travelers take their 3 capsules on alternate days, but many did not follow the other recommendations. Electronic monitoring of compliance provides more accurate results than questionnaires. Emphasis must be put on motivating the travelers to take the vaccine as recommended.