Generally, a short-acting beta-2 agonist (SABA) delivered via metered-dose inhaler (MDI) is recommended for quick relief of asthma symptoms. However, in the PeRson EmPowered Asthma RElief (PREPARE) pragmatic trial, 67% of patients reported having used a nebulizer for SABA administration. To understand preferences, experiences, and decision making regarding the use of nebulizers in Black and Latinx adults with uncontrolled asthma. We interviewed 40 of the 1,201 PREPARE patients employing a matrix analysis. Those interviewed were Black (n = 20) and Latinx (n = 20) adults with uncontrolled asthma seeking primary or specialty care in clinics throughout the United States. Data were analyzed used a Rapid Assessment Procedures qualitative methodology, informed by grounded theory. Substudy participants, on average, reported using a nebulizer 3.5 times/wk. Daily use was common, and frequency ranged from less than daily to up to 6 times daily. Nearly all participants reported a longstanding history of nebulizer use. Participants tended to use their nebulizer at home, and some shared it with others in the home. Many reported preferring a nebulizer over an MDI for relief of severe symptoms and to avoid emergency room visits or hospitalizations. The extent to which cost affected nebulizer use varied among participants. Despite asthma guideline recommendations that MDIs be used rather than nebulizers for SABA administration, nebulizer use was common among PREPARE study participants. Clinicians should explore patients' history and experiences with nebulizer use as part of evaluation of asthma control.