Despite effective treatments and interventions, asthma continues to affect children's health-related quality of life (QOL). This study explored factors affecting QOL of children with asthma and their caregivers. A mixed-model design was used. Children (7-17 years) completed the Paediatric Asthma Quality of Life Questionnaire, and parents/caregivers completed the Paediatric Asthma Caregiver's Quality of Life Questionnaire. These surveys focused on activity limitations, emotional function, and child symptoms. The sample included 104 children and 104 caregivers. Analysis showed emergency department (ED) visits as a significant predictor of QOL for children in the domains of Physical Activity, Emotional, and Symptoms. Increased ED visits and reliever medication use predicted lower emotional QOL and physical QOL for parents, whereas increased use of controller medications predicated improved physical QOL. Factors contributing to QOL, along with characteristics of those with the lowest QOL indicators, have been determined. Identification of interventions to reduce ED visits warrants further investigation. Copyright © 2019 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.