Background: Guidelines recommend a differentiation of difficult-to-treat asthma from severe asthma. However, this might be complex and to which extent this distinction is achievable in clinical practice remains unknown. Objective: To evaluate to which degree a systematic evaluation protocol enables a differentiation between severe versus difficult-to-treat asthma in patients in specialist care on high intensity asthma treatment, i.e. potentially severe asthma. Methods: All adult asthma patients seen in four respiratory clinics over one year were screened prospectively for asthma severity. Patients with difficult-to-control asthma according to ERS/ATS criteria (high–dose inhaled corticosteroids/oral corticosteroids) underwent systematic assessment to differentiate severe asthma patients from those with other causes of poor asthma control: objective confirmation of the asthma diagnosis as well as assessment of treatment barriers and comorbidities. Results: Overall, 1034 asthma patients were screened, of whom 175 (16.9%) had difficult-to-control asthma. 117 of these accepted inclusion, and completed systematic assessment. Asthma diagnosis was objectively confirmed in 88%. Sub-optimal adherence (42.5%), inhaler errors (31.5%) and unmanaged comorbidities (66.7%) were common. After primary assessment, 12% (14/117) fulfilled strict criteria for severe asthma. Moreover, 56% (66/117) were instantly classified as difficult-to-treat asthma due to poor adherence/inhaler technique. Finally, an ´overlap’ group of 32% (37/117) were identified with patients being adherent and displaying correct inhaler technique, but had unmanaged comorbidities —potentially fitting into both the difficult-to-treat and severe group. Conclusion: Only a minority of patients with difficult-to-control asthma were found to have severe asthma after primary systematic assessment. Nevertheless, strict categorisation of severe vs. difficult-to-treat asthma seems to pose a challenge.