Background <p>Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) poses a significant global threat due to limited therapeutic options and high rates of associated mortality. CRAB-related bloodstream infections (BSIs) in intensive care units (ICUs) represent a major clinical challenge. This study aimed to investigate the clinical outcomes of CRAB-BSIs in ICU settings and evaluate the prognostic effect of different antimicrobial regimens.</p> Methods <p>This multicenter, retrospective observational study was conducted at five medical centers in Taiwan and included 393 critically ill patients with CRAB-BSIs between January 2015 and December 2019. Clinical and microbiological outcomes were analyzed. Multivariable regression analysis was used to identify independent prognostic factors for day-28 mortality.</p> Results <p>The most common causes of CRAB-BSIs were pneumonia (42.5%) and catheter-related infections (38.7%). The day-28 mortality rate following BSI onset was 56.5%. A higher sequential organ failure assessment (SOFA) score independently predicted increased day-28 mortality. Colistin-based therapy was associated with improved survival outcomes in the original (adjusted hazard ratio [aHR], 0.56; 95% confidence intervals (CI), 0.35–0.88) and time-window bias-adjusted (aHR, 0.59; 95% CI, 0.37–0.94) cohorts. Among patients with pneumonia-related CRAB-BSIs, colistin-based therapy did not significantly improve day-28 survival, whereas sulbactam-based therapy showed survival benefit (aHR, 0.37; 95% CI, 0.15–0.91). Neither carbapenem-based nor tigecycline-based therapies demonstrated a mortality benefit on day 28.</p> Conclusion <p>CRAB-BSIs are associated with high mortality in critically ill patients. In settings where novel antibiotics are not available, colistin-based therapy was associated with improved clinical outcomes. Among patients with pneumonia-related CRAB-BSIs, sulbactam-based therapy was associated with lower mortality.</p>