Among Western countries, France has the highest incidence of imported malaria cases, mostly from travellers visiting Sub-Saharan Africa (SSA). Despite related high costs of imported malaria assumed by the public French national health insurance system (FHS), the latter does not reimburse travellers for malaria chemoprophylaxis (MC). This study aims to analyzes, from the FHS perspective, the cost-effectiveness of a 65% reimbursement of MC costs (MC 65%) for French resident travellers, under the assumption that this reimbursement would lead to increased recourse to MC. For that purpose, a decision tree model was developed with variables obtained from the literature, including incidence of malaria among travellers in the absence of MC, probabilities of recourse to MC, MC effectiveness and costs and medical expenses for a case of imported malaria. Data analysis of 1,434,675 travellers to SSA in 2005 estimated, for MC 65% vs. MC 0%, incidence of malaria cases to be 3836 malaria cases (21 deaths)/year vs. 6321 cases (34 deaths)/year, respectively, and cost of Euro 47,071,687/year vs. Euro 17,416,955/year. Incremental cost of MC 65% related to MC 0% was Euro 11,933 per malaria case prevented and Euro 2,281,133 per malaria-related death prevented. Results generated by this model, which can be adapted for other European countries, should be an incentive for the FHS to favourably consider MC 65% for French residents travelling to SSA.