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Summary: Background: While non‐eosinophilic asthmatics are usually considered poorly responsive to inhaled corticosteroids (ICSs), studies assessing a step‐down of ICS in this specific population are currently lacking. Objectives: To assess the proportion of non‐eosinophilic asthmatics in whom ICS may be withdrawn without any clinical degradation and to determine the predictive markers of a failure to stop treatment with ICS. Methods: This prospective study was completed by 36 non‐eosinophilic asthmatics, defined by sputum eosinophils <3% and blood eosinophils <400/μL. In these patients, whichever the baseline asthma control level, the dose of ICS was gradually reduced every 3 months until they met the failure criteria or successfully discontinued ICS for 6 months. The failure criteria were an ACQ score ≥1.5 with an increase from baseline >0.5 or a number of severe exacerbations during the study which was greater than the number during the year prior to the baseline visit. Receiver‐operating characteristic (ROC) curves were constructed to assess predictors of a failure to stop ICS. This study is registered with ClinicalTrials.gov, number NCT02169323. Results: In 14 patients (39%), ICSs were completely withdrawn, and in 10 further patients (28%), ICS were stepped‐down to a reduced ICS dose without any deterioration of asthma control and exacerbation rate. Baseline predictors of a failure to stop ICS were a greater age (area under ROC curve [ROC AUC] and [95% CI]: 0.77 [0.62‐0.93]) and elevated blood eosinophils (ROC AUC [95% CI]: 0.77 [0.61‐0.93]). After the first step‐down of ICS, the best predictor was an elevated blood eosinophil count (ROC AUC [95% CI]: 0.85 [0.72‐0.99]). Conclusions & Clinical Relevance: Withdrawing or reducing the dose of ICS is feasible in two‐thirds of non‐eosinophilic asthmatics irrespective of baseline asthma control. An elevated blood eosinophil count may predict the failure to stop ICS. [ABSTRACT FROM AUTHOR]