Abstract Background. Effective hand-washing can prevent nosocomial infections, particularly in high-risk areas of the hospital. There are few clinical studies of the efficacy of specific hand-cleansing agents in preventing the transmission of pathogens from health care workers to patients. Methods. For eight months, we conducted a prospective multiple-crossover trial involving 1894 adult patients in three intensive care units (ICUs). In a given month, the ICU used a hand-washing system involving either chlorhexidine, a broad-spectrum antimicrobial agent, or 60 percent isopropyl alcohol with the optional use of a nonmedicated soap; in alternate months the other system was used. Rates of nosocomial infection and hand-washing compliance were monitored prospectively. Results. When chlorhexidine was used, there were 152 nosocomial infections, as compared with 202 when the combination of alcohol and soap was used (adjusted incidence-density ratio [IDR], 0.73; 95 percent confidence interval, 0.59 to 0.90). The l...