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We evaluated changes in the epidemiology of catheter-related bloodstream infections (CRBSIs) between 1996 and 2012 in a tertiary care centre in Israel. The cohort included 1754 episodes of CRBSI. The incidence of CRBSIs decreased throughout the study period, whereas 30-day mortality following bacteraemia increased. There was a linear shift toward predominance of Gram-negative bacilli throughout the study period (p for trend<0.001). In 1996, 68% (68/100) of CRBSIs were caused by Gram-positive cocci, whereas in 2012 77.8% (28/26) were caused by Gram-negative bacilli. The shift towards Gram-negative CRBSIs and the associated mortality mandates that empirical treatment for CRBSIs be directed by local epidemiology.