The objective of this prospective observational study was to determine the influence of femoral and central internal jugular venous catheters on the incidence of catheter-related bacteremia (CRB). We included patients admitted to a 12-bed polyvalent medico-surgical intensive care unit over 4 years who received one or more femoral or central internal jugular venous catheters. We diagnosed 16 cases of CRB in 208 femoral catheters and 22 in 515 central internal jugular venous catheters. We found a higher incidence of CRB with femoral (9.52 per 1,000 catheter days) than with central internal jugular venous access (4.83 per 1,000 catheter days; risk ratio = 1.93; 95% confidence interval: 1.03-3.73; P = 0.04). Central internal jugular venous access could be considered a safer route of venous access than femoral access in minimizing the risk of central venous catheter-related bacteremia.