Recent guidelines from the Centers for Disease Control and Prevention (CDC) recommend the use of alcohol-based hand sanitizers rather than traditional hand washing. This clinical trial compared these strategies on patient infection rates, nurses’ skin conditions, and microbial counts in neonatal intensive care units. Adjusted results showed no difference in patient infection rates or microbial counts, but skin condition was improved using the alcohol-based product. The discussion compares these findings with existing research and the confounding factors associated with measured infection rates. The authors recommend adopting the CDC recommendations as a system-based method to improve hand hygiene practices.