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Purpose: The identification of risk factors associated with uncontrolled moderate-to-severe asthma is important to improve asthma outcomes. Aim of this study was to identify risk factors for uncontrolled asthma in United States cohort using electronic health record (EHR)-derived data. Patients and Methods: In this retrospective real-world study, de-identified data of adolescent and adult patients (≥ 12 years old) with moderate-to-severe asthma, based on asthma medications within 12 months prior to asthma-related visit (index date), were extracted from the Optum® Humedica EHR. The baseline period was 12 months prior to the index date. Uncontrolled asthma was defined as ≥ 2 outpatient oral corticosteroid bursts for asthma or ≥ 2 emergency department visits or ≥ 1 inpatient visit for asthma. A Cox proportional hazard model was applied. Results: There were 402,403 patients in the EHR between January 1, 2012, and December 31, 2018, who met the inclusion criteria and were analyzed. African American (AA) race (hazard ratio [HR]: 2.08), Medicaid insurance (HR: 1.71), Hispanic ethnicity (HR: 1.34), age of 12 to < 18 years (HR 1.20), body mass index of ≥ 35 kg/m2 (HR: 1.20), and female sex (HR 1.19) were identified as risk factors associated with uncontrolled asthma (P < 0.001). Comorbidities characterized by type 2 inflammation, including a blood eosinophil count of ≥ 300 cells/μL (as compared with eosinophil < 150 cells/μL; HR: 1.40, P < 0.001) and food allergy (HR: 1.31), were associated with a significantly higher risk of uncontrolled asthma; pneumonia was also a comorbidity associated with an increased risk (HR: 1.35) of uncontrolled asthma. Conversely, allergic rhinitis (HR: 0.84) was associated with a significantly lower risk of uncontrolled asthma. Conclusion: This large study demonstrates multiple risk factors for uncontrolled asthma. Of note, AA and Hispanic individuals with Medicaid insurance are at a significantly higher risk of uncontrolled asthma versus their White, non-Hispanic counterparts with commercial insurance. [ABSTRACT FROM AUTHOR]