Patient safety in ambulatory care settings is receiving increased attention. Based on interviews and focus groups with patients, providers, and staff at ten patient-centered medical homes, this qualitative study explored perceived facilitators and barriers to improving safety in ambulatory care. Participants identified several safety issues, including communication failures and challenges with medication reconciliation, and noted the importance of health information systems and dedicated resources to advance patient safety. Patients also emphasized the importance of engagement in developing safety solutions. A recent PSNet perspective discusses patient safety challenges in ambulatory care, particularly during the COVID-19 pandemic.