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Importance: The role of the operating room (OR) airborne environment in the incidence of surgical site infections (SSI) has ranked behind patient and perioperative team-related factors associated with risk for SSI. Emerging evidence demonstrates that the design and performance of the OR environment impacts the airborne microbiome both within the sterile field and at tables where instruments and implants are exposed. However, the correlation between OR air quality and the risk of SSI continues to be challenged. Objective: To determine if improving the asepsis of the airborne environment in ORs contributes to reduced SSI rates. Design: The performance of air delivery systems in fourteen operating rooms was evaluated using the Environmental Quality Indicator (EQI) risk picture method to identify potential improvements to airflow management that reduce airborne contamination and operating costs. SSI rates for colon and abdominal hysterectomy procedures were tracked in these ORs for 39 months before and after improvements were implemented. SSI rates were also tracked for the same time frame for six control ORs in which no improvements were made. Airborne microbial data was collected. Setting: Twenty ORs in an academic medical center, Midwest USA. A convenience sample of all surgical patients, de-identified, was used in the twenty ORs studied. Results: SSI rate was reduced from 8.4% to 5.7% (p=.0039) in ORs in which improvements were implemented. Reduction of SSI rate in control ORs was not significant (p=.76). Fewer airborne microbes were detected in areas of OR with improvements (p<.0001). Conclusion: Areas for environmental quality improvement in ORs was identified and mapped by relative risk of contamination. Implementation of these improvements resulted in decreased microbial contamination and contributed to significant reduction in surgical site infection.