Every year, 2 million patients in the United States suffer with at least 1 hospital-acquired infection resulting in an estimated 99,000 deaths annually. The purpose of this exploratory single case study was to explore strategies healthcare managers in U.S. hospitals used to reduce hospital-acquired infections. The study included face-to-face, semistructured interviews with 5 healthcare managers from a hospital in Maryland who were successful in reducing these infections. The conceptual framework was human capital theory. Field notes, hospital documents, and transcribed interviews were analyzed to identify themes regarding strategies used by healthcare managers. The data analysis and coding process resulted in 5 major themes: use of HAI-related data; implementation of detailed cleaning method; implementation of define, measure, analyze, implement, and control; education and training of staff; and implementation of the Antimicrobial Stewardship Program. The findings from this study might benefit healthcare managers in implementing and sustaining successful strategies to reduce hospital-acquired infections. The implications for positive social change included reducing hospital-acquired infections, thereby leading to fewer hospitalization days for patients and a faster recovery time to return to normal life. Reducing hospital acquired infections might reduce patient deaths related to the infections.