OBJECTIVE: To describe challenges in inpatient pediatric quality and safety during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a previous qualitative study, our team sought to broadly describe changes in pediatric inpatient care during the pandemic. For both that study and this ancillary analysis, we purposefully sampled participants from community and children’s hospitals in the 6 US states with the highest COVID-19 hospitalization rates from March to May 2020. We recruited 2 to 3 participants from each hospital (administrators, front-line physicians, nurses, caregivers) for semistructured interviews. We used constant comparative methods to identify themes regarding quality and safety challenges during the pandemic. RESULTS: We interviewed 30 participants from 12 hospitals. Participants described several impacts to clinical workflows, including decreased direct clinician-patient interactions and challenges to communication, partly addressed through innovative use of telehealth technology. Participants reported changes in the discharge and transfer process (eg, discharges, difficulties accessing specialized facilities). Participants also described impacts to hospital operations, including changes in quality monitoring and operations (eg, decreased staff, data collection), increased health risks for clinicians and staff (eg, COVID-19 exposure, testing delays), and staff and supply shortages. Participants voiced concerns that negative quality and safety impacts could include increased risk of preventable safety events and hospital readmissions, and decreased patient engagement, education, and satisfaction. CONCLUSIONS: We identified several impacts to clinical workflows and hospital operations during the pandemic that may have affected inpatient pediatric care quality and safety. Our findings highlight potentially important areas of focus for planning pandemic recovery, preparing for future pandemics, and conducting future research on inpatient pediatric quality and safety.