Background: Frequent exacerbations are an important cause of morbidity in patients with severe asthma. Objective: Our aim was to identify factors associated with frequent exacerbations in a large well-characterized severe asthma population and determine whether factors differed in patients treated with and without maintenance oral corticosteroids (OCS).Methods: Adults with severe asthma from specialized asthma centers across the UK were recruited to the UK Severe Asthma Registry (UKSAR). Demography, co-morbidities and physiological measurements were collected. We conducted univariable and multivariable logistic regression analyses to identify factors associated with frequent exacerbations, defined as ≥3 exacerbations treated with high-dose systemic corticosteroids in the past year.Results: Of 1592 patients with severe asthma from the UKSAR, 1137 (71%) were frequent exacerbators (FE) and 833 (52%) were on maintenance OCS. FE were more likely to be ex-smokers, have gastroesophageal reflux disease (GERD), higher Asthma Control Questionnaire-6 (ACQ-6) score and blood eosinophilia. Multivariable regression analyses showed ACQ-6 score >1.5 (OR 4.25, p<0.001), past smoking history (OR 1.55, p=0.024) and FeNO >50ppb (OR 1.54, p=0.044) were independently associated with frequent exacerbations. Past smoking history correlated with frequent exacerbations only in patients on maintenance OCS (OR 2.25, p=0.004), whereas ACQ-6 score >1.5 was independently associated with frequent exacerbations in those treated with and without maintenance OCS (OR 2.74, p=0.017 and OR 6.42, p<0.001, respectively). Conclusion: Several factors were associated with frequent exacerbations in a large UK severe asthma registry population. High ACQ-6 score had the strongest association with frequent exacerbations irrespective of maintenance OCS status.