Central-line-associated bloodstream infections (CLABSIs) are responsible for ∼1/3 of all deaths from healthcare-associated infections in the United States. Of these, multidrug-resistant organisms (MDROs) are responsible for 20% to 67%. However, whether catheter removal affects clinical outcomes for MDRO CLABSIs has not been studied. Our objective was to determine the relationship between failure to remove a central venous catheter (CVC) and 30-day all-cause mortality in patients with MDRO CLABSIs. We used a retrospective cohort from Barnes-Jewish Hospital (1/1/2009–10/1/2015) to study patients with a multidrug-resistant Staphylococcus aureus, Enterococcus species, Enterobacteriaceae, Acinetobacter species, or Pseudomonas aeruginosa CLABSI. Risk factors for 30-day mortality, including catheter removal, were assessed for association with 30-day mortality using Cox proportional hazards models. The CLABSIs were assessed prospectively at the time of occurrence by infection prevention specialists. A total of 430 patients met inclusion criteria, 173 (40.2%) with Enterococcus, 116 (27.0%) Enterobacteriaceae, 81 (18.8%) S aureus, 44 (10.2%) polymicrobial, 11 (2.6%) P aeruginosa, and 5 (1.2%) Acinetobacter CLABSIs. Removal of a CVC occurred in 50.2% of patients, of which 4.2% died by 30 days (n = 9). For patients whose CVC remained in place, 45.3% died (n = 97). Failure to remove a CVC was strongly associated with 30-day all-cause mortality with a hazard ratio of 13.5 (6.8–26.7), P < .001. Other risk factors for 30-day mortality included patient comorbidities (cardiovascular disease, congestive heart failure, cirrhosis), and being in an intensive care unit at the time of MDRO isolation. Failure to remove a CVC was strongly associated with 30-day all-cause mortality for patients with MDRO CLABSIs in this single center retrospective cohort. This suggests that patients presenting with MDRO CLABSIs should all undergo CVC removal.