A significant unremitting increase in the incidence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infections in a 500-bed acute care community teaching hospital prompted reevaluation of the efficacy of the infection control measures used. A well-accepted, low-iodine, antimicrobial soap was used to replace a liquid natural handsoap in two areas with the highest incidence of MRSA—the intensive care unit, and a medical division.Over a two-year period, an analysis was made of the effect of soap replacement on nosocomial infections and pathogens. Soap changeover occurred at the midpoint of the two-year period. From year to year, the nosocomial MRSA rate decreased 80% (t test, P=0.005). Other pathogens that demonstrated a dramatic decrease included methicillin-sensitive Staphylococcus aureus (MSSA), infections where no pathogens were isolated, and various gram-negative infections. Categories of nosocomial infections that decreased included surgical wound infections, primary bacteremias, and respiratory tract infections. The overall nosocomial infection rate of the two combined areas decreased 21.5%, representing a year-to-year savings of $109,500. As a result, the decision was made to install the low-iodine hand-soap permanently at all sinks within the hospital.