Aim: To describe the relationship between loss of control events in preschoolers with asthma and persistence of disease. Methods: We reviewed medical records of children <6 years diagnosed with asthma in 2018 to assess loss of control events during three years of follow-up. Asthma persistency was defined by redeem of short-acting β2-agonist or asthma controllers within one year after the end of follow-up. Logistic regression models were applied to analyse the association between loss of control events and persistence of asthma. Results: We included 172 patients (median age 1.8 years), whereof 126 (73.3%) experienced a loss of control event and 87 (50.6%) had asthma one year after the end of follow-up. Any loss of control event was associated with persistence of asthma adjusted for controller treatment at inclusion, prior exacerbations, atopic comorbidity and caesarean section: aOR, 10.9 (95% CI, 3.9–34.6), p < 0.001. This was also significant restricted to events in the first year of follow-up: 3.52 (1.50–8.67), p < 0.01 and among children only experiencing one event: 6.4 (1.7–27.3), p = 0.01. Conclusion: Loss of control events during a 3-year period among preschoolers with asthma are closely related to disease persistency, which may aid clinicians to assess risk of persistent asthma in young children.