The prevalence of central venous catheters (CVCs) for hemodialysis remains high and, despite infection-control protocols, predisposes to bloodstream infections (BSIs). Stratified, cluster-randomized, quality improvement initiative. All in-center patients with a CVC within 211 facility pairs matched by region, facility size, and rate of positive blood cultures (January to March 2011) at Fresenius Medical Care, North America. Incorporate the use of 2% chlorhexidine with 70% alcohol swab sticks for exit-site care and 70% alcohol pads to perform "scrub the hubs" in dialysis-related CVC care procedures compared to usual care. The primary outcome was positive blood cultures for estimating BSI rates. Comparison of 3-month baseline period from April 1 to June 30 and follow-up period from August 1 to October 30, 2011. Baseline BSI rates were similar (0.85 vs 0.86/1,000 CVC-days), but follow-up rates differed at 0.81/1,000 CVC-days in intervention facilities versus 1.04/1,000 CVC-days in controls (P = 0.02). Intravenous antibiotic starts during the follow-up period also were lower, at 2.53/1,000 CVC-days versus 3.15/1,000 CVC-days in controls (P < 0.001). Cluster-adjusted Poisson regression confirmed 21%-22% reductions in both (P < 0.001). Extended follow-up for 3 successive quarters demonstrated a sustained reduction of bacteremia rates for patients in intervention facilities, at 0.50/1,000 CVC-days (41% reduction; P < 0.001). Hospitalizations due to sepsis during 1-year extended follow-up were 0.19/1,000 CVC-days (0.069/CVC-year) versus 0.26/1,000 CVC-days (0.095/CVC-year) in controls (∼27% difference; P < 0.05). Inability to capture results from blood cultures sent to external laboratories, underestimation of sepsis-specific hospitalizations, and potential crossover adoption of the intervention protocol in control facilities. Adoption of the new catheter care procedure (consistent with Centers for Disease Control and Prevention recommendations) resulted in a 20% lower rate of BSIs and intravenous antibiotic starts, which were sustained over time and associated with a lower rate of hospitalizations due to sepsis.