Health care-associated infections (HAIs) increase morbidity, mortality, and hospital costs. Multiple organizations have worked independently to reduce HAIs. Regional collaborative efforts to reduce HAIs have been less common but may be particularly effective. The authors describe a statewide multicomponent approach implemented by the Iowa Healthcare Collaborative (IHC) to reduce HAIs. IHC’s initiatives helped providers improve patient care by becoming engaged in specific projects, improving communication, sharing data, and implementing best practices. Other states could use this approach as a model to engage clinicians in patient safety initiatives and thereby accelerate the rate at which clinical care and health care outcomes are improved.