A prospective study on hospital-acquired infection (HAI) was undertaken in the eight-bed neurosurgical intensive care unit (NSICU) of a teaching hospital in Rome, Italy. All patients admitted for >48 h between January 2002 and December 2004 were included. The infection control team collected the following data from all patients: demographic characteristics, patient origin, diagnosis, severity score, underlying diseases, invasive procedures, HAI, isolated micro-organisms and antibiotic susceptibilities. Overall, 323 patients were included in the study. Mean age was 55.5 years (range 17-91), and mean American Society of Anesthesiologists' score was 2.88. Seventy (21.7%) patients developed 132 NSICU HAIs: 43 pneumonias, 40 bloodstream infections (BSIs), 30 urinary tract infections (UTIs), 10 cases of meningitis associated with an external ventricular drain (EVD) and nine surgical site infections (SSIs). The SSI rate was high (5.6%), but a reduction was achieved during the three-year period. There were 7.2 bloodstream infection episodes per 1000 days of device exposure; 11.00 pneumonias per 1000 days of mechanical ventilation and 4.5 UTIs per 1,000 days of urinary catheterisation. Among patients with an EVD, the SSI relative risk was 11.3 [95% confidence intervals (CI) 4.2-30.6; P<0.01]. Sixty-one (18.9%) patients died. Logistic regression analysis showed that mortality was significantly associated with infection [odds ratio (OR)=2.28; 95%CI 1.11-4.71; P=0.02] and age (OR=1.04; 95%CI 1.01-1.06; P=0.002). Candida spp. were the leading cause of UTIs (40.0%) and the third most common cause of BSIs (12.7%). Antibiotic-resistant pathogens included meticillin-resistant staphylococci (77.5%), carbapenem-resistant Pseudomonas aeruginosa (36.4%), and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (75.0%). Although the overall incidence of infection (21.7%) was within the range of published data, the associated mortality, the increasing severity of illness of patients, and the emergence of multi-drug-resistant organisms shows the need to improve infection control measures.