Madagascar joined “Roll Back Malaria” in 2002. During the last 15 years, the Malagasy government has received significant external funds to implement malaria operational strategies. Madagascar recorded progress due to scale-up interventions. Nevertheless, the number of malaria cases has increased significantly since 2012. This paper aims to estimate the cost of the national malaria program corresponding to the national strategic plan from 2009 to 2013 and the cost-effectiveness of two malaria control strategies (indoor spraying insecticide -IRS- and insecticide treated nets -ITN), using household survey data from 2014 in two districts in Madagascar. The cost-effectiveness of IRS and ITN was estimated at the district level. For this purpose, the total cost of the national malaria control program (NMCP) and the cost of cases averted were calculated. The NMCP has cost USD 46,588,677 or USD 2.1 per capita per year from 2009 to 2013. The implementation of IRS costs about 4 times more than ITN. The cost effectiveness rate (CER) of IRS per case averted was higher (USD 297.6) than the CER of ITN (USD 56.5 in Ankazobe and USD 31.4 in Brickaville. The CER per Daly averted was USD 531.2 for IRS, USD 53.9 (in Brickaville) and USD 99.6 (in Ankazobe) for ITN. Compared to GDP per capita, ITN strategy appeared highly cost-effective and IRS cost-effective. The cost of IRS being high and less effective in the Malagasy context, a budgetary impact analysis should be relevant before a potential extension of that strategy.