To study the impact of a multimodal infection control program on the rate of nosocomial infections at a 550-bed tertiary care center. Before and after the implementation of an infection control program, the rate of nosocomial infection was recorded in time-interval prevalence studies. Hand hygiene compliance was studied before and after the intervention. As a surrogate marker of compliance, the amount of alcohol-based hand rub consumed before the intervention was compared with the amount consumed after the intervention. The intervention included additional staff for infection control, repeated instructions for hand hygiene, new guidelines for preoperative antibiotic prophylaxis, and isolation of patients infected or colonized with multidrug-resistant bacteria. The rate of nosocomial infection decreased from approximately 11.7% to 6.8% in 2 years. The rate of hand hygiene compliance increased by 20.0%; it was 59.0% before the intervention and increased to 79.0% afterward. These results correlate with data on the consumption of alcohol-based hand rub, but not with data on the use of antibiotics. Within 2 years, a multimodal infection control program intervention such as this one may reduce the rate of nosocomial infection at a tertiary care center by more than one-third and improve both the quality of care and patient outcomes. It may also generate considerable savings. Therefore, such programs should be promoted not only by hospital epidemiologists but also by hospital administrators.