Background <p>Critically ill patients with cirrhosis face an elevated risk of mortality. The hemoglobin-to-red blood cell distribution width ratio (HRR) has emerged as a potential biomarker in various critical illnesses. However, the prognostic significance of longitudinal HRR changes in patients with cirrhosis remains underexplored. Therefore, this study aimed to investigate the association between HRR trajectory patterns and in-hospital mortality in this population.</p> Methods <p>Data were extracted from the Medical Information Mart for Intensive Care IV, version 3.1 (MIMIC-IV v3.1), and the eICU-Collaborative Research Database (eICU-CRD). Group-based trajectory modeling was applied to identify distinct HRR trajectory patterns. The primary outcome was in-hospital mortality. Kaplan–Meier analysis was used to estimate survival rates, and multivariate Cox regression was employed to evaluate associations. Subgroup and sensitivity analyses were conducted to test the robustness of the findings.</p> Results <p>A total of 1,826 patients from MIMIC-IV and 669 patients from eICU-CRD were included. Three distinct HRR trajectories were identified: stable low trajectory (trajectory 1), descending high trajectory (trajectory 2), and descending moderate trajectory (trajectory 3). Using the trajectory 1 group as the reference, after adjusting for potential confounders, trajectory 2 (HR: 0.56; 95% CI: 0.42–0.76) and trajectory 3 (HR: 0.63; 95% CI: 0.51–0.77) were both associated with a reduced risk of in-hospital mortality. Subgroup and sensitivity analyses further confirmed the robustness of these results.</p> Conclusion <p>Continuous monitoring of HRR trajectories is crucial for prognostic evaluation and risk stratification among critically ill patients with cirrhosis, as persistently low HRR levels are associated with a significantly increased risk of in-hospital mortality.</p>