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Blood-borne pathogen exposure (BBPE) represents a significant safety and resource burden, with more than 380,000 events reported annually across hospitals in the United States. The perioperative environment is a high-risk area for BBPE, and efforts to reduce exposures are not well defined. A multidisciplinary group of nurses, surgical technologists, surgeons, and employee health specialists created a BBPE prevention bundle to reduce Occupational Safety and Health Administration (OSHA) recordable cases.Mandatory double gloving, a safety zone, engineered-sharps injury prevention devices, and clear communication when passing sharps were implemented in an evidence-based fashion at one institution. Days between exposures and total number of exposures were monitored. Analysis by specialty, role, location, type of injury, and timing was performed.During fiscal year (FY) 2015, 45 cases were reported. During the first year of implementation, cases decreased to 38 (a 15.6% decrease; p0.65). In the postimplementation period (FY 2017), only 21 cases were reported (an additional 44.7% decrease; p0.12), for a total decrease of 53.3% (p0.01). The mean number of days between injuries significantly increased (2.5 to 16.3) over the study period. For FY 2017, the main cause of BBPE was needlestick while suturing (47.6%); fellows and attendings combined had the most injuries (52.4%); among divisions, pediatric surgery (19.0%), operating room staff (19.0%), and orthopedics (19.0%) had the most events.A comprehensive and multidisciplinary approach to employee safety, focused on reduction of BBPE resulted in a significant progressive annual decrease of injuries among perioperative staff.