Preventing healthcare-acquired infections (HAIs) remains a patient safety priority. Based on a collaborative effort led by the Society for Healthcare Epidemiology in America (SHEA) and the Infectious Diseases Society of America (IDSA), this practice guideline builds on previous work and summarizes strategies to prevent common HAIs (i.e., catheter-associated urinary tract infections, Clostridium difficile infections, surgical site infections, central line-associated bloodstream infections, methicillin-resistant Staphylococcus aureus infections, and ventilator-associated pneumonia) as well as strategies to increase hand hygiene to prevent HAIs.