Hand hygiene prevents cross infection in hospitals, but compliance with recommended instructions is commonly poor. We attempted to promote hand hygiene by implementing a hospital-wide programme, with special emphasis on bedside, alcohol-based hand disinfection. We measured nosocomial infections in parallel. We monitored the overall compliance with hand hygiene during routine patient care in a teaching hospital in Geneva, Switzerland, before and during implementation of a hand-hygiene campaign. Seven hospital-wide observational surveys were done twice yearly from December, 1994, to December, 1997. Secondary outcome measures were nosocomial infection rates, attack rates of methicillin-resistant Staphylococcus aureus (MRSA), and consumption of handrub disinfectant. We observed more than 20,000 opportunities for hand hygiene. Compliance improved progressively from 48% in 1994, to 66% in 1997 (p<0.001). Although recourse to handwashing with soap and water remained stable, frequency of hand disinfection substantially increased during the study period (p<0.001). This result was unchanged after adjustment for known risk factors of poor adherence. Hand hygiene improved significantly among nurses and nursing assistants, but remained poor among doctors. During the same period, overall nosocomial infection decreased (prevalence of 16.9% in 1994 to 9.9% in 1998; p=0.04), MRSA transmission rates decreased (2.16 to 0.93 episodes per 10,000 patient-days; p<0.001), and the consumption of alcohol-based handrub solution increased from 3.5 to 15.4 L per 1000 patient-days between 1993 and 1998 (p<0.001). The campaign produced a sustained improvement in compliance with hand hygiene, coinciding with a reduction of nosocomial infections and MRSA transmission. The promotion of bedside, antiseptic handrubs largely contributed to the increase in compliance.