Background: Infectious airborne and surface pathogens constitute a substantial and poorly explored source of patient subclinical illness and infections. With that in mind, a system of advanced air purification technology was designed to destroy the DNA and RNA of all bacteria, fungi, and viruses. This study compares the effects of advanced air purification technology versus high efficiency particulate air filtration with respect to certain metrics of health care economics and resource utilization at a large, community-based, urban hospital. Our hypothesis was that the use of the advanced air purification technology would decrease health care durations of stay, lead to fewer nonhome discharges, and decrease hospital charges. Methods: After the installation of advanced air purification technology, 3 resultant air purification "zones" were established: zone C, a control floor with high efficiency particulate air filtration; zone B, a mixed high efficiency particulate air and advanced air purification technology floor; and zone A, a comprehensive advanced air purification technology remediation. This study included nonbariatric surgical patients admitted to any zone between December 2017 and December 2018, with reported case mix index on discharge. We analyzed hospital duration of stays, discharge destination, and hospital charges with adjustment for severity of illness using the case mix index. The likelihood of mortality, health care-associated infection, and readmission for each study zone was examined using logistic regression adjusting for case mix index, age, sex, and source of admission. Results: The study included 1,002 patients across the 3 zones, with mean age of 55.8 years (53.7% female), average case mix index of 1.98, and mortality of 1.7%. Compared with zone C, patients in zones A and B demonstrated decreased hospital stays, a greater percentage of home discharges (86.5e87.8% vs 64.7%), and less hospital charges. In addition, logistic regression modeling performed on 999 study patients showed that the likelihood of mortality, hospital-acquired infections, and readmissions did not differ among the 3 zones. A trend toward a lesser incidence of hospital-acquired infections was noted in zones A and B (0.40% and 0.48%, respectively) when compared with zone C (0.63%). Conclusion: Patients in the advanced air purification technology zones demonstrated statistically significant improvements in durations of stay, discharge to home, and costs after adjusting for case mix index. In addition, a trend toward fewer hospital-acquired infections in advanced air purification technology zones was noted. These findings suggest that environmental factors may affect key clinical and economic outcomes, supporting further research in this important and largely unexplored area.