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Objectives: To update the Agency for Healthcare Research and Quality (AHRQ) Evidence Report Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies: Volume 6-Prevention of Healthcare-Associated Infections on quality improvement (QI) strategies to increase adherence to preventive interventions and/or reduce infection rates for central line-associated bloodstream infections (CLABSI), ventilator-associated pneumonia (VAP), surgical site infections (SSI), and catheter-associated urinary tract infections (CAUTI)., Data Sources: MEDLINE®, CINAHL®, and Embase® were searched from January 2006 to January 2012 for English-language studies with sample size ≥100 patients, a defined baseline period, and reported statistical analysis for adherence and/or infection rates. Articles from the previous report were screened and those meeting selection criteria were included., Review Methods: We sought studies that evaluated the following QI strategies to improve adherence to evidence-based preventive interventions and/or reduce healthcare-associated infection (HAI) rates: audit and feedback; financial incentives, regulation, and policy; organizational change; patient education; provider education; and provider reminder systems. Data were abstracted by a single reviewer and fact-checked by a second. Outcomes were adherence to preventive interventions, infection rates, adverse outcomes, and cost savings. Study quality was assessed using relative rankings based on study design, adequacy of statistical analysis, length of followup, reporting and analysis of baseline and postintervention adherence and infection rates, and implementation of the intervention independent of other QI efforts. Combinations of QI strategies were assessed, not individual strategies. Strength of evidence was judged according to the AHRQ Methods Guide., Results: Sixty-one articles yielded 71 analyses at the infection level, including 9 articles (10 analyses) from the 2007 report, which evaluated the use of one or more QI strategies to improve adherence or infection rates and also controlled for confounding or secular trend. Twenty-six analyses were performed on CLABSI, 19 on VAP, 15 on SSI, and 11 on CAUTI. There were 34 analyses on adherence, of which 31 (91%) showed significant improvement. There were 63 analyses of infection rates, of which 42 (67%) showed significant improvement., Conclusions: There is moderate strength of evidence across all four infections that both adherence and infection rates improve when either audit and feedback plus provider reminder systems or audit and feedback alone is added to the base strategies of organizational change and provider education. There is low strength of evidence that adherence and infection rates improve when provider reminder systems alone are added to the base strategies. There was insufficient evidence for reduction of HAI in nonhospital settings, cost savings for QI strategies, and the nature and impact of the clinical contextual factors.