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To better understand the operating room as a system and to identify system features that influence patient safety, we performed an analysis of operating room patient care using a prospective observational technique.A multidisciplinary team comprised of human factors experts and surgeons conducted prospective observations of 10 complex general surgery cases in an academic hospital. Minute-to-minute observations were recorded in the field, and later coded and analyzed. A qualitative analysis first identified major system features that influenced team performance and patient safety. A quantitative analysis of factors related to these systems features followed. In addition, safety-compromising events were identified and analyzed for contributing and compensatory factors.Problems in communication and information flow, and workload and competing tasks were found to have measurable negative impact on team performance and patient safety in all 10 cases. In particular, the counting protocol was found to significantly compromise case progression and patient safety. We identified 11 events that potentially compromised patient safety, allowing us to identify recurring factors that contributed to or mitigated the overall effect on the patient's outcome.This study demonstrates the role of prospective observational methods in exposing critical system features that influence patient safety and that can be the targets for patient safety initiatives. Communication breakdown and information loss, as well as increased workload and competing tasks, pose the greatest threats to patient safety in the operating room.