In this study the influence of hand hygiene compliance on healthcare-associated infections was investigated, when an already high level of compliance (>80%) was increased even further to >95%. The program to increase hand hygiene compliance (Clean In, Clean Out) was focused on cleaning hands upon entering and leaving patient rooms. An improvement of hand hygiene compliance by 10% led to a significant hospital wide reduction of healthcare-associated infections by 6%. For a facility with 853 beds this means an estimated 197 fewer infections, 22 fewer deaths, and savings of about US$ 5 mio.