Following the rapid increase of infections due to carbapenemase-producing Enterobacteriaceae (CPE) in Italy, the national surveillance of bloodstream infections (BSI) due to CPE (Klebsiella pneumoniae and Escherichia coli) was instituted in 2013. All CPE-BSI cases reported to the surveillance in the years 2014–17 were analysed in order to investigate incidence rate (IR), trend, main individual characteristics and enzymes involved in CPE resistance. Throughout this period, 7,632 CPE-BSI cases (IR: 3.14/100,000 inhabitants) were reported from all 21 regions and autonomous provinces in Italy, with an increasing number of reported cases (2014: 1,403; 2015: 1,838; 2016: 2,183; 2017: 2,208). CPE-BSI cases mainly occurred in subjects aged over 60 years (70.9%) and more frequently in males (62.7%) than in females. Most of the cases originated in hospitals (87.2%), mainly in intensive care units (38.0%), and were associated with central or peripheral venous catheter use (23.9%) or with urinary tract infections (21.1%). Almost all CPE-BSI (98.1%) were due to K. pneumoniae carrying the K. pneumoniae carbapenemase (KPC) enzyme (95.2%). These data show that carbapenemase-producing K. pneumoniae are endemic in our country, causing a high number of BSI and representing a threat to patient safety.