The proportion of nosocomial infections potentially preventable under routine working conditions remains unclear. We performed a systematic review to describe multi-modal intervention studies, as well as studies assessing exogenous cross-infection published during the last decade, in order to give a crude estimate of the proportion of potentially preventable nosocomial infections. The evaluation of 30 reports suggests that great potential exists to decrease nosocomial infection rates, from a minimum reduction effect of 10% to a maximum effect of 70%, depending on the setting, study design, baseline infection rates and type of infection. The most important reduction effect was identified for catheter-related bacteraemia, whereas a smaller, but still substantial potential for prevention seems to exist for other types of infections. Based on these estimates, we consider at least 20% of all nosocomial infections as probably preventable, and hope that this overview will stimulate further research on feasible and cost-effective prevention of nosocomial infections for daily practice.