ObjectivesFrance is the Western country with the highest number of imported malaria cases. This study evaluates the cost and effectiveness of the potential reimbursement of drugs for malaria chemoprophylaxis (CP). It targets travelers with medical insurance in France who are heading to endemic regions in sub-Saharan Africa (SSA), the cost of which is currently fully borne by these travelers. Patients and methodsA decision-tree model was built to assess the cost-effectiveness of three CP reimbursement strategies compared to the current strategy of non-reimbursement from the French National Health Insurance (NHI) perspective. The three strategies targeted either (1) all travelers to SSA (2) travelers of African origin traveling to visit friends and relatives (VFR) and (3) all travelers to West and Central Africa (WCA). Base-case analysis is complemented with deterministic and probabilistic sensitivity analyses (PSA). ResultsReimbursement of CP would lead to a decrease in malaria cases. The base-case incremental cost per additional malaria case prevented (ICER) for strategies 1, 2 and 3 is estimated at € 34,623, € 15,136 and € 23,640, respectively. PSA confirms our results, showing that reimbursement has a very high probability of being cost-effective, especially under strategies 2 and 3. ConclusionReimbursement of malaria CP by the French NHI could be cost-effective and have a positive effect on malaria prevention in France. Restricting reimbursement to VFRs allows lower ICERs but does not seem feasible in the current French context, while targeting travelers to WCA, who are at higher risk for malaria, could be a reasonably efficient policy.