The Centers for Disease Control and Prevention (CDC) define a healthcare-associated infection (HAI) as: " A] localized or systemic condition resulting from an adverse reaction to the presence of an infectious agent(s) or its toxin(s). There must be no evidence that the infection was present or incubating at the time of admission to the acute care setting." The CDC estimates that in 2002 there were 1.7 million HAI and 99,000 HAI-associated deaths in hospitals. The four largest categories of HAI, responsible for more than 80 percent of all reported HAI, are central line-associated bloodstream infections (CLABSI, 14%), ventilator associated pneumonia (VAP, 15%), surgical site infections (SSI, 22%), and catheter-associated urinary tract infections (CAUTI, 32%). In a CDC report, national costs of HAI were estimated, based on 2002 infection rates and adjusted to 2007 dollars using the Consumer Price Index for inpatient hospital services. Estimates of the total annual direct medical costs of HAI for U.S. hospitals ranged from $35.7 billion to $45 billion. The prevention and reduction of HAI is a top priority for the U.S. Department of Health and Human Services. A call to action for the elimination of HAI has been issued jointly by the Association for Professionals in Infection Control and Epidemiology, Inc., the Society for Healthcare Epidemiology of America, the Infectious Diseases Society of America, the Association of State and Territorial Health Officials, the Council of State and Territorial Epidemiologists, the Pediatric Infectious Diseases Society, and the CDC. In a consensus statement issued by these groups, a plan for the elimination of HAI includes the promotion of adherence to evidence-based practices through partnering, educating, implementing, and investing. In 2003, the Institute of Medicine (IOM) published a report, Priority Areas for National Action: Transforming Health Care Quality. The report identified 20 clinical topics for which there are quality concerns because of the gap between knowledge of the topic and integration of that knowledge into the clinical setting. In response to the IOM report, the Agency for Healthcare Research and Quality (AHRQ) initiated a series of technical reviews on quality improvement strategies focused on improving the quality of care for the IOM's 20 priority areas. This systematic review updates the AHRQ Evidence Report Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies: Volume 6-Prevention of Healthcare Associated Infections. From here on, this report is referred to as the 2007 report. The objective of that evidence review was to identify QI strategies that successfully increase adherence to effective preventive interventions and reduce infection rates for CLABSI, VAP, SSI, and CAUTI. The current review expands the settings to be considered from primarily hospitals to include ambulatory surgery centers, freestanding dialysis centers, and long-term care facilities, where the prevention of HAI needs to be addressed as well. Where applicable, the current report also applies the recommendation of a report prepared for AHRQ by RAND Health in which the impact of context on the effectiveness of patient safety practices is assessed. The context of an intervention can have an important impact on whether preventive interventions are adopted. Key Questions for this report follow. Key Question 1. Which quality improvement strategies are effective in reducing the following healthcare-associated infections - Central line-associated bloodstream infections (CLABSI), Ventilator-associated pneumonia (VAP), Surgical site infections (SSI), Catheter-associated urinary tract infections (CAUTI)? Key Question 2. What is the impact of the health care context on the effectiveness of quality improvement strategies, including reducing infections and increasing adherence to preventive interventions?