Asthma is the most common chronic condition of childhood. Hospitalizations and emergency department (ED) visits for asthma are more frequently experienced by minority children and adolescents and those with low socioeconomic status. To reduce asthma-related hospitalizations and ED visits for Medicaid-insured pediatric patients residing in Hamilton County, Ohio. From January 1, 2010, through December 31, 2015, a multidisciplinary team used quality-improvement methods and the chronic care model to conduct interventions in inpatient, outpatient, and community settings in a large, urban academic pediatric hospital in Hamilton County, Ohio. Children and adolescents aged 2 to 17 years who resided in Hamilton County, had a diagnosis of asthma, and were Medicaid insured were studied. Interventions were implemented in 3 phases: hospital-based inpatient care redesign, outpatient-based care enhancements, and community-based supports. Plan-do-study-act cycles allowed for small-scale implementation of change concepts and rapid evaluation of how such tests affected processes and outcomes of interest. The study measured asthma-related hospitalizations and ED visits per 10 000 Medicaid-insured pediatric patients. Data were measured monthly on a rolling 12-month mean basis. Data from multiple previous years were used to establish a baseline. Data were tracked with annotated control charts and with interrupted time-series analysis. Of the estimated 36 000 children and adolescents with asthma in Hamilton County (approximately 13 000 of whom are Medicaid insured and 6000 of whom are cared for in Cincinnati Children's Hospital primary care practices), asthma-related hospitalizations decreased from 8.1 (95% CI, 7.7-8.5) to 4.7 (95% CI, 4.3-5.1) per 10 000 Medicaid patients per month by June 30, 2014, a 41.8% (95% CI, 41.7%-42.0%) relative reduction. Emergency department visits decreased from 21.5 (95% CI, 20.6-22.3) to 12.4 (95% CI, 11.5-13.2) per 10 000 Medicaid patients per month by June 30, 2014, a 42.4% (95% CI, 42.2%-42.6%) relative reduction. Improvements were sustained for the subsequent 12 months. The proportion of patients who were rehospitalized or had a return ED visit for asthma within 30 days of an index hospitalization was reduced from 12% to 7%. The proportion of patients with documented well-controlled asthma in this study's primary care population increased from 48% to 54%. An integrated, multilevel approach focused on enhancing availability and accessibility of treatments, removing barriers to adherence, mitigating multidomain risks, augmenting self-management, and creating a collaborative relationship between the family and the health care system was associated with improved asthma outcomes for a population of Medicaid-insured pediatric patients. Similar models used in accountable care organizations or across patient panels and with other chronic conditions could be feasible and warrant evaluation.