Background: The NHSN is the nation’s largest surveillance system for healthcare-associated infections. Since 2011, acute-care hospitals (ACHs) have been required to report intensive care unit (ICU) central-line–associated bloodstream infections (CLABSIs) to the NHSN pursuant to CMS requirements. In 2015, this requirement included general medical, surgical, and medical-surgical wards. Also in 2015, the NHSN implemented a repeat infection timeframe (RIT) that required repeat CLABSIs, in the same patient and admission, to be excluded if onset was within 14 days. This analysis is the first at the national level to describe repeat CLABSIs. Methods: Index CLABSIs reported in ACH ICUs and select wards during 2015–2108 were included, in addition to repeat CLABSIs occurring at any location during the same period. CLABSIs were stratified into 2 groups: single and repeat CLABSIs. The repeat CLABSI group included the index CLABSI and subsequent CLABSI(s) reported for the same patient. Up to 5 CLABSIs were included for a single patient. Pathogen analyses were limited to the first pathogen reported for each CLABSI, which is considered to be the most important cause of the event. Likelihood ratio χ2 tests were used to determine differences in proportions. Results: Of the 70,214 CLABSIs reported, 5,983 (8.5%) were repeat CLABSIs. Of 3,264 nonindex CLABSIs, 425 (13%) were identified in non-ICU or non-select ward locations. Staphylococcus aureus was the most common pathogen in both the single and repeat CLABSI groups (14.2% and 12%, respectively) (Fig. 1). Compared to all other pathogens, CLABSIs reported with Candida spp were less likely in a repeat CLABSI event than in a single CLABSI event (P < .0001). Insertion-related organisms were more likely to be associated with single CLABSIs than repeat CLABSIs (P < .0001) (Fig. 2). Alternatively, Enterococcus spp or Klebsiella pneumoniae and K. oxytoca were more likely to be associated with repeat CLABSIs than single CLABSIs (P < .0001). Conclusions: This analysis highlights differences in the aggregate pathogen distributions comparing single versus repeat CLABSIs. Assessing the pathogens associated with repeat CLABSIs may offer another way to assess the success of CLABSI prevention efforts (eg, clean insertion practices). Pathogens such as Enterococcus spp and Klebsiella spp demonstrate a greater association with repeat CLABSIs. Thus, instituting prevention efforts focused on these organisms may warrant greater attention and could impact the likelihood of repeat CLABSIs. Additional analysis of patient-specific pathogens identified in the repeat CLABSI group may yield further clarification.