Multi-drug-resistant gram-negative rods (MRGN) are associated with increased morbidity and mortality. Little is known about the epidemiology of this group of pathogens in endemic situations. The aim of this study was to determine the epidemiology of MRGN in our facility during a 3-year period. Prospective surveillance of any patient colonized or infected with a MRGN during hospital stay from 2002 to 2004 was performed. Patients proven to harbour extended beta-lactamase (ESBL)-producing bacteria as well as cystic fibrosis (CF) patients were excluded. After culture of MRGN, patients were considered positive until three consecutive samples from all previously affected locations had been tested negative. Five hundred and three case-patients were enrolled accounting for 8081 isolation days and an incidence of 0.43 per 1000 patient days with an average length of stay of 37.5 days (average duration of isolation: 22.6 days). Sixty-six percent of case-patients were known to be positive at the time of admission. Fifty-one percent of MRGN were acquired within the hospital. The most frequently detected species was Pseudomonas aeruginosa. There were 108 case-patients with pan-resistant pathogens. Eight of 169 (4.7%) screened contact patients were found to be MRGN positive. In our hospital cross-transmission of MRGN seems to occur less frequently than cross-transmission of MRSA (9.0%) or ESBL (11.1%). To prevent nosocomial transmission it is recommended to isolate patients colonized or infected with MRGN in our hospital in single rooms. Because there are many immunocompromised patients in our facility we will continue our current infection control management until more data concerning MRGN are available.