During a 22-month period at a 500-bed teaching hospital, 1,565 rooms that had housed patients infected with multidrug-resistant pathogens were decontaminated using hydrogen peroxide vapor. Hydrogen peroxide vapor decontamination required a mean time of 2 hours and 20 minutes, compared with 32 minutes for conventional cleaning. Despite the greater time required for decontamination, hydrogen peroxide vapor decontamination of selected patient rooms is feasible in a busy hospital with a mean occupancy rate of 94%.