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This review of empirical literature focuses on the design of operating rooms (ORs) by investigating the physical environmental features of ORs associated with patient and staff outcomes.Many ORs built more than 30 years ago remain operational today. However, most are inadequately designed to handle the equipment, processes, and people that a contemporary OR needs to accommodate. However, the evidence base for designing ORs has been sorely lacking, and little guidance exists on how OR design can improve safety and performance outcomes.A literature search was conducted using PubMed and the university’s linked databases. The inclusion criteria included peer-reviewed journal articles that reported some aspect of the physical environment of ORs along with outcomes. The study included empirical studies as well as nonempirical best practice papers.This literature review uncovered 211 articles. The main themes that emerged include OR design-related factors, ventilation, temperature and humidity, acoustical environment, lighting, and materials. Some environmental threats to patient safety in the OR include frequent door openings, clutter, poor air quality, surface contamination, and noise. Further, staff performance and satisfaction were impacted by factors such as the OR layout and equipment and furniture ergonomics.This literature review provides an overview of the research organized into design-focused topic areas to support decision-making by architects and designers. This article highlights gaps in the research and identifies areas where best practice and design assumptions need to be evaluated using rigorous design research.