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Background: The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50‐>80%) in preschool children has been reported. There are limited studies exploring its relationship to respiratory symptoms and how it predicts persistent wheeze. We aimed to assess the association with respiratory symptoms in preschool‐aged children with LCI and determine its utility in predicting persistent wheeze. Methods: LCI was measured in a subcohort of the CHILD Cohort Study at age 3 years using SF6 multiple breath washout test mass spectrometry. Respiratory symptom phenotypes at age 3 were derived from children's respiratory symptoms reported by their parents. Responses were used to categorize children into 4 symptom groups: recurrent wheeze (3RW), recurrent cough (3RC), infrequent symptoms (IS), and no current symptoms (NCS). At age 5 years, these children were seen by a specialist clinician and assessed for persistent wheeze (PW). Results: At age 3 years, 69% (234/340) had feasible LCI. Excluding two children with missing data, 232 participants were categorized as follows: 33 (14%) 3RW; 28 (12%) 3RC; 17 (7%) IS; and 154 (66%) NCS. LCI z‐score at age 3 years was highest in children with 3RW compared to 3RC (mean (SD): 1.14 (1.56) vs. 0.09 (0.95), p <.01), IS (mean (SD): −0.14 (0.59), p <.01), and NCS (mean (SD): −0.08 (1.06), p <.01). LCI z‐score at age 3 was predictive of persistent wheeze at age 5 (PW) (AUROC: 0.87). Conclusions: LCI at age 3 was strongly associated with recurrent wheeze at age 3, and predictive of its persistence to age 5. [ABSTRACT FROM AUTHOR]