ABSTRACTSurgical site infections (SSIs) frequently involve resident bacteria (eg, Staphylococcus aureus) on the patient’s skin. Strategies to help prevent SSIs include removing soil and transient microorganisms from the skin before surgery. Preoperative decolonization, preoperative bathing, and application of an effective skin antiseptic at the surgical site are components of a multimodal approach to reducing microorganisms to subpathogenic levels. As members of an interdisciplinary team, perioperative RNs are essential in the development and implementation of SSI prevention bundles to promote patient safety. This article discusses recommendations from the AORN “Guideline for preoperative patient skin antisepsis” for decolonization protocols, preoperative bathing, and selection of surgical site antiseptics. A scenario describes the process a facility team uses to determine components of an SSI prevention bundle after recognizing an increase in infections from multidrug‐resistant organisms.