Central venous catheterization is a common practice in the management of critically ill patients and is associated with various complications, such as Bloodstream Infections (BSI), which are major determinants of increased morbidity, mortality and healthcare expenses. Few studies have addressed factors that predict mortality in patients with this complication. The aim of this study was to investigate factors associated with mortality in patients with Central Venous Catheter (CVC)-related BSI in an intensive care unit of a tertiary care hospital in the Federal District, Brazil. This was a retrospective and observational study, in which all CVC-related BSI that occurred between January 2008 and December 2010 were reviewed. We obtained demographic, clinical, biochemical and microbiological data from medical records and investigated its association with mortality during ICU stay. There were 4,504 ICU admissions during the study period and 68 were complicated by CVC-related BSI (4.09 per 1000 catheter-days), most due to gram-negative organisms (45.6%). Overall mortality was 59.7%. Death risk was significantly associated with mechanical ventilation (OR 27.8, 95% CI 3.28-250, p<0.001), the mean number of invasive devices other than the CVC (1.44 Vs 2.37 in controls Vs cases, p<0.001) and increased serum levels of urea (mean value of 44.2 mg dL in survivors vs. 73.9 mg dL in non-survivors, p = 0.001). Mortality was not associated with other clinical or biochemical features, neither with microbiological variables, although lethality was high among patients with gram-positive infections (77% Vs 58.33% for fungi and 54.83% for gram-negative). CVC-related BSI was associated with high absolute mortality, which was predicted by mechanical ventilation and a higher number of invasive devices other than the CVC. Knowledge of local factors predictive of mortality is critical for planning strategies to reduce death risk associated with this complication.