The risk of a needle stick or sharps injury in the operating room (OR) is high due to conditions such as minimal physical protective measures, frequent transfer of sharps, and reliance on human attention and skill for injury avoidance. An ergonomic process improvement project was initiated at a large metro teaching hospital to identify ergonomic risk factors for these OR injuries. To maximize the engagement of the front- end users, an ergonomic process improvement (EPI) team was developed, consisting of representatives from participating OR teams, an employee health nurse and two ergonomists. Surveys, observations, and interviews were conducted to quantify injury risk for the OR teams, evaluate barriers to best practice adherence, and identify opportunities for targeted interventions. Risk mapping was completed for the surgeons, surgical techs and OR nurses identifying double gloving and safe passing zone as areas in need of improvement. Through observation and interviews, researchers identified physical factors relating to musculoskeletal pain and cognitive factors leading to distractions as safety risk concerns. The overall success of the EPI was the engagement of the OR teams and surgeons in the process of identifying risk factors and potential opportunities for ergonomic solutions related to cognitive workload, physical workload, teamwork, and work design for injury prevention. The risk factors identified will provide the basis for developing targeted, effective interventions for eliminating injuries from needles and sharps within the OR.