OBJECTIVE: To compare the risk and exposure-adjusted central line-associated bloodstream infection (CLABSI) rates between racial and ethnic groups. DESIGN: Retrospective cohort study. SETTING: 15 network hospitals in Illinois and Michigan (Part of OSF HealthCare). PATIENTS: Patients of all age groups who had a central line inserted and removed during the same hospitalization between 01/2018 and 06/2023. METHODS: CLABSI rates/1000 Central line days of the four major racial and ethnic categories (Hispanic, non-Hispanic White [NHW], non-Hispanic Black [NHB], and non-Hispanic others) were analyzed by generalized Poisson regression. Confounding variables included in the regression model based on a directed acyclic graph and included age group, insurance class, language, ICU admission, diagnostic cohorts (obesity, diabetes, dialysis, cancer, neutropenia), and line usage (blood products, chemotherapy, total parenteral nutrition). RESULTS: 27,674 central lines (244,889 catheter days) on 23,133 unique patients (median age 64 years, 8% pediatric patients) were included in the analysis. Overall, the CLABSI rate was 1.070/1000 Central line days. 76% of the study population was NHW, 17% NHB, and 4% Hispanic. After adjusting for confounding variables, Hispanic patients had higher CLABSI rates than NHW (IRR 1.89, 95% CI 1.15-3.10, CONCLUSION: Disparities in hospital-associated conditions persist even after controlling for patient-level risk factors and exposures, with Hispanic patients at the highest risk.