Nosocomial infections are a major part of the problem of reemerging pathogens causing infectious diseases, affecting 5% of patients hospitalized in the United States during 1995. We assessed the medical and economic effects on the overall nosocomial infection rate of an intervention that provided an enhanced, integrated infection control program, including an in-house molecular typing laboratory capability to rapidly assess microbial clonality. Data on nosocomial infections for 24 months prior to the change in approach to infection control were compared with data from the 24 months immediately following implementation of the new program. Infections per 1,000 patient-days and percentage of hospitalized patients in whom nosocomial infection developed were assessed. Overall, nosocomial infections per 1,000 patient-days decreased more than 10% (P = .027), and percentage of patients with nosocomial infection decreased 23% during the post-intervention period compared with the previous control 24 months. This translated to a mean reduction of some 270 patients per year with nosocomial infection, and lowering of actual health care costs for our institution by $4,368,100 over the 2 years of the intervention.