Central line-associated bloodstream infection (CLABSI) rates increased substantially in the United States following the emergence of COVID-19 and subsequent surges. The pandemic resulted in hospital capacities being exceeded and crisis standards of care being implemented for sustained periods. As COVID-19 rates in the United States began to stabilize, some facilities did not return to previous CLABSI rates, indicating a change in practices that had a longer-term impact on CLABSI prevention. The authors' large health care system observed similar increases in CLABSI following the emergence of COVID-19, prompting investigation and intervention in the form of a quality improvement project. To identify changes related to ongoing increases in CLABSI, an assessment team conducted standardized on-site assessments at 11 facilities. Site assessments were considered an intervention, as they involved rigorous preassessment investigations and interviews, case reviews, practice observations, on-site staff interviews, and postassessment support for additional interventions. Nine facilities had enough postassessment data to analyze the impact of intervention. The overall CLABSI rate (infections per 1000 line days) at the 9 facilities in the 6 months prior to intervention was 1.42, and the postassessment rate in the 6 months following intervention was 0.44. This indicates the effectiveness of facility-specific investigation followed by targeted performance improvements to reduce the rate of CLABSI.