Few models for systematically targeting patient safety risks in large health systems exist. For this quality improvement study encompassing five large health care delivery systems, key informants were interviewed at seven affiliated outpatient sites in an effort to understand why ambulatory care accounted for 30-35% of annual medical malpractice costs and missed or delayed diagnoses comprised about 50% of liability risk associated with office practices. Analysis revealed eight common patient safety risk domains; the single most important was communication and follow-up of diagnostic test results. The authors recommend employing their targeted approach to safety improvements in other large health systems.