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Surgical site infections are unintended consequences of surgery that can cause harm to patients and place financial burdens on health care organizations. Extrinsic factors in the OR—including health care providers’ behavior and practices that modify air movement, the physical environment, equipment, or surgical instruments—can increase microbial contamination. Microbes can be transported into the surgical incision by airborne or contact routes and contribute to a surgical site infection. Simple practices to prevent infection—such as minimizing airborne particles and contaminants, maintaining equipment according to the manufacturer’s recommendations, cleaning and disinfecting the environment and surgical instruments, and performing proper hand hygiene—can reduce the degree of microbial contamination. Perioperative leaders and health care providers can help decrease the patient’s risk of surgical site infection with proactive preventive practices that break the chain of infection.