Background: Media reports have implicated mefloquine as a contributor to adverse health effects experienced by military members serving in areas where chloroquine-resistant malaria is endemic. A systematic retrospective review has been undertaken to evaluate the health effects seen in members who received mefloquine for chemoprophylaxis against malaria. Methods: Medical records of Regular Canadian Forces (CF) personnel who served in Somalia between 1992 and 1993 were reviewed by trained data extractors. All health effects recorded during treatment with mefloquine were assigned ICD-10-CA codes. Data extractors also noted if the effect has been reported with mefloquine, and rated the severity of the effect. Cohen's kappa was calculated to determine concordance between extractors, and descriptive statistics used to report the health effects seen. Results: The majority of the 1413 subjects identified were male (96%). A total of 5019 adverse health effects were recorded in the medical records, most of which were mild in severity. At least one adverse effect which could potentially have been related to mefloquine was reported in 74.7% ( n = 1056) of subjects. Of the adverse effects recorded, 21 were classified by the data extractors as major (18 cases affecting the nervous system and 3 cardiovascular system effects). These results are consistent with those reported in other populations. Conclusions: The results of this study have been applied to guide development of policies governing the provision of chemoprophylaxis during subsequent military missions. In particular, resources have been allocated to formalize the counselling provided to members regarding antimalarials and prevention of malaria infection.