Background: Acute-care hospitals in the United States are required to submit 6 healthcare-associated infection (HAI) metrics to the CMS for reporting and performance purposes prior to payment. We examined the association between HAI rate trends and hospital-onset bloodstream infection (HO-BSI) rate trends across a large, multihospital health system. Methods: HO-BSI events were identified across 52 hospitals attributable to Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, or Candida spp using the NHSN Lab ID event definition of ≥day 4 of admission. We compared the performance from January 2016 to March 2019 for HO-BSI and the 6 NHSN-defined HAIs: central-line–associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, abdominal hysterectomy surgical site infections (SSIs), and colon SSI. We calculated 2 “infection composite scores” to account for the 6 HAIs based on all observed or predicted events (score 1) and an average of the 6 HAI standardized infection ratios (SIRs; score 2). We normalized both measures to 1 for a 12-months rolling baseline. We evaluated the HO-BSI rate change over time and compared it to the change in the infection score over the same period. We compared the change in the 12-month rolling rates of the 2 HAI scores and the HO-BSI rate. Results: During the 39-month period, 3,288 HO-BSI events occurred over 9,775,118 patient days. The source of HO-BSI events included S. aureus (33.5%), P. aeruginosa (10.2%), E. coli (19.7%), K. pneumoniae (13.8%), and Candida spp (22.8%). HO-BSI event rates decreased by 17.3% from 12-month rolling baseline to last 12 months (3.70 vs 3.06 per 10,000 patient days). Similarly, 7,648 HAI events were observed, with the source of events being Clostridioides difficile (57.0%), CAUTI (15.1%), CLABSI (12.8%), MRSA (7.0%), colon SSI (6.4%), and abdominal hysterectomy SSI (1.7%). The 2 HAI scores and the HO-BSI rate all showed a notable decrease from the 2016 baseline period (Fig. 1). The reductions in the HAI scores were both strongly correlated with the reduction in the HO-BSI rate, with the HAI score 1 having a stronger correlation (r = 0.949; P < .001) than was observed for HAI score 2 (r = 0.867; P < .001). Conclusions: Utilization of a HO-BSI measure may prove useful as a correlated but distinct marker of infection prevention improvement or trends. HO-BSI could be useful as an objective electronically obtainable measure to assist in the evaluation of performance within and across facilities.