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BackgroundHealthcare-associated infections (HAIs) constitute a significant financial strain on healthcare systems across the world, with surgical site infections (SSIs) being the costliest form. Despite the existence of diverse sources of infection in the operating room (OR), current literature focuses on human and procedural sources of contamination that could lead to an infection. Comparatively, the OR built environment is understudied as a potential disease transmission interface between the environment, patients, and surgical staff. This systematic literature review aims to investigate how the physical characteristics and components of the built environment impact airflow, infection risk, aerosols, particle counts, contamination, and pathogens in operating rooms.Methods and FindingsLiterature searches were conducted in the PubMed and Web of Science Core Collection databases on December 21, 2020, ultimately retrieving 2,965 articles after duplicates were removed. During abstract screening, all abstracts were independently reviewed by two authors and conflicts were resolved by a third author. All articles published since January 1, 2010, that reported primary data investigating an aspect of the built environment inside an OR in relation to airflow, contamination, and/or infection for which the full text in English was available were included. This resulted in the inclusion of 138 articles, which includes studies conducted in ORs during active surgeries, computer modeling studies, and simulations in which a real OR was used for a mock surgical procedure. Six major built environment categories were identified based on the collected literature: OR layout, disinfection systems, surgical lights, doors, ventilation, and portable airflow devices. A survey created on Qualtrics software was used to record the aspect of the built environment and the outcome of each study, as well as the relationship between the two.ConclusionsWhile OR ventilation has been studied extensively, the OR built environment as a whole is understudied in relation to airflow, contamination, and infection. The current literature is inconsistent in both its findings and subsequent recommendations, making it difficult to inform hospital design in the context of SSIs. No articles were identified that discussed respiratory infection transmission in the OR, and very few addressed healthcare worker (HCW) safety in relation to the OR built environment. The significant discrepancies in the literature identified in this review highlight the need for future studies that assess the quality and bias of these studies before firm recommendations can be made. Future work should also focus on addressing the lack information regarding respiratory infection transmission in the OR, especially in the context of HCW safety.