Centers for Disease Control and Prevention (CDC) risk adjustment methods for central-line-associated bloodstream infections (CLABSI) only adjust for type of intensive care unit (ICU). This cohort study explored risk factors for CLABSI using 2 comorbidity classification schemes, the Charlson Comorbidity Index (CCI) and the Chronic Disease Score (CDS). Our study supports the need for additional research into risk factors for CLABSI, including electronically available comorbid conditions.