OBJECTIVES Montelukast 4mg (MTL-4) is an add-on therapy for asthmatic infants. Given the quality and exhaustivity of the data, French claims data (SNIIR-AM) is a relevant tool to investigate MTL-4 effectiveness in infants. The objective was to compare the effectiveness of MTL-4, associated or not with ICS, vs. ICS without MTL-4, on health outcomes of infants with mild to moderate uncontrolled asthma.  METHODS Infants (6-24 months) receiving ≥ 2 consecutive dispensing of respiratory drugs from 2010 to 2011, and presenting an initial exacerbation within 6 months of the first dispensing were preselected. Asthma-related outcomes included hospitalizations, dispensing of oral corticosteroids, addition of short-acting beta agonists to existing respiratory therapy, switch to a higher ICS dosage, or nebulized CS. The studied groups were infants receiving MTL-4 +/- ICS (MTL-4 group) and infants receiving ICS without MTL-4 (ICS group). The two groups were matched, e.g. on initial therapy before initial exacerbation and past asthma related hospitalization. The two groups were compared, as to the occurrence of a new exacerbation and the total number of exacerbations during the 6 month follow-up following initial exacerbation. We also compared health care utilization between both groups. RESULTS Among 115,489 infants (mean age: 13.9 months; 62.9% boys), 4,477 infants of the MTL-4 group were matched with 13,386 infants of the ICS group. In multivariate analysis, the risk of a new exacerbation was lower in infants of MTL-4 group compared to infants in ICS group (HR=0.91, IC95% [0.87;0.95]). The total number of exacerbations did not differ between the 2 groups during the 6-month follow-up (p=0,8617), neither the cost of asthma management (344€ for MTL-4 group vs. 308€ for ICS group, p=0.1410). CONCLUSIONS MTL-4 and ICS appear to be comparable therapeutic strategies, with similar effects on exacerbation and equivalent costs. The SNIIR-AM allows conducting comparative effectiveness research.