Objective To assess the risk factors associated with CR-BSI development in critically ill patients with non-tunneled, non-cuffed central venous catheters (CVC) and the prognosis of the episodes of CR-BSI. Design and setting; prospective, observational, multicenter study in nine Spanish Hospitals. Patients All subjects admitted to the participating ICUs from October 2004 to June 2005 with a CVC. Interventions None. Measurement and results Overall, 1,366 patients were enrolled and 2,101 catheters were analyzed. Sixty-six episodes of CR-BSI were diagnosed. The incidence of CR-BSI was significantly higher in CVC compared with peripherically inserted central venous catheters (PICVC) without significant differences among the three locations of CVC. In the multivariate analysis, duration of catheterization and change over a guidewire were the independent variables associated with the development of CR-BSI whereas the use of a PICVC was a protective factor. Excluding PICVC, 1,598 conventional CVC were analyzed. In this subset, duration of catheterization, tracheostomy and change over a guidewire were independent risk factors for CR-BSI. A multivariate analysis of predictors for mortality among 66 patients with CRSI showed that early removal of the catheter was a protective factor and APACHE II score at the admission was a strong determinant of in-hospital mortality. Conclusions Peripherically inserted central venous catheters is associated with a lower incidence of CR-BSI in critically ill patients. Exchange over a guidewire of CVC and duration of catheterization are strong contributors to CR-BSI. Our results reinforce the importance of early catheter removal in critically ill patients with CR-BSI.