Background: Allergy immunotherapy (AIT) is the only disease- modifying treatment for respiratory allergy. The study primary objective was to evaluate the impact of sublingual liquid AIT (SLIT) in a real-world setting on the worsening of asthma.Method: A cohort analysis with propensity score weighting was performed using the French nationwide healthcare insurance sys-tem “SNDS” database paired to the database of AIT dispensation of Stallergenes Greer. The inclusion period was from 2010 to 2013. Patients­dispensed­at­ least­ 9­ vials,­ or­>1­ deliveries,­of ­SLIT­were­ con-sidered exposed. Unexposed patients were selected among those with allergic rhinitis (AR) treatment and without history of AIT exposure, as identified in the SNDS database. Index date was the first dispensing of SLIT or AR treatment and patients were followed until first event, death or 31/12/2018. Inclusion and exclusion criteria were aligned with SLIT indication. Onset or worsening of asthma were defined as the first occurrence of a specific pharmacy dispensation, hospital dis-charge summaries or long- term diseases (LTDs) for asthma in the main analysis; pharmacy dispensation was omitted for a more specific, sec-ondary definition. Analyses were stratified on the pre- existing mild or moderate asthma to differentiate between the onset and worsening of asthma. Adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using an adjusted Cox regression model with inverse probability of treatment weighting (IPTW).Results: A total of 101,345 exposed (SLIT) and 333,082 unexposed patients (control) were included, with a follow-up of 2,537,074 and 690,740 person-years respectively. SLIT was associated with a sig-nificantly lower risk of onset or worsening of asthma versus con-trol, according to main (HR: 0.78, 95% CI 0.77–0.78) and secondary definition (HR: 0.72, 95% CI 0.69–0.76). Among patients without pre-existing asthma (Table 1 and Figure 1), SLIT was associated with a significantly lower risk of occurrence of asthma versus con-trol, according to main (HR: 0.78, 95% CI 0.77–0.79) and secondary definition (HR: 0.80, 95% CI 0.73–0.87); in this population, the risk reductions were largest for patients with grass (main HR 0.65, 95% CI 0.64–0.67) and mites allergy (main HR 0.75, 95% CI 0.74–0.77). Results were consistent amongst all age groups.Conclusion: In this national real-world study with the largest number of person-years of follow-up in the field of AIT to date, SLIT was ef-fective in reducing the risk of asthma onset< Réduire