Background Critically ill patients are at marked risk of hospital-acquired infections, which increase patients' morbidity and mortality. Registered nurses are the main health care providers of physical care, including hygiene to reduce and prevent hospital-acquired infections, for hospitalized critically ill patients. Objective To investigate a new patient hand hygiene protocol designed to reduce hospital-acquired infection rates and improve nurses' hand-washing compliance in an intensive care unit. Methods A preexperimental study design was used to compare 12-month rates of 2 common hospital-acquired infections, central catheter--associated bloodstream infection and catheter-associated urinary tract infection, and nurses' hand-washing compliance measured before and during use of the protocol. Results Reductions in 12-month infection rates were reported for both types of infections, but neither reduction was statistically significant. Mean 12-month nurse hand-washing compliance also improved, but not significantly. Conclusions A hand hygiene protocol for patients in the intensive care unit was associated with reductions in hospital-acquired infections and improvements in nurses' hand-washing compliance. Prevention of such infections requires continuous quality improvement efforts to monitor lasting effectiveness as well as investigation of strategies to eliminate these infections.