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ObjectiveThe ROX index, combining oxygenation and respiratory rate, is widely used to assess respiratory failure. However, its prognostic value in critically ill patients with chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to explore the association between the ROX index and mortality in ICU patients with COPD.MethodsThis retrospective cohort study included patients with COPD from two large databases: MIMIC-IV (v3.1) and eICU-CRD (v2.0). The ROX index was calculated within the first 24 hours of ICU admission. The primary outcome was in-hospital mortality, with ICU mortality and 28-day mortality as secondary outcomes. Cox regression models, Kaplan-Meier survival curves, restricted cubic spline (RCS) analysis, and subgroup analyses were used to evaluate the association between ROX and mortality.ResultsA total of 1,639 patients from the MIMIC-IV cohort and 2,170 from the eICU-CRD cohort were included. In multivariable Cox regression, a higher ROX index was independently associated with a lower risk of in-hospital mortality (MIMIC-IV: HR = 0.96, 95% CI: 0.93-0.98; eICU-CRD: HR = 0.95, 95% CI: 0.92-0.98). Similar associations were observed for ICU and 28-day mortality. RCS analysis demonstrated a linear negative correlation between ROX and the risk of death. Subgroup analyses showed consistent results across various clinical strata. The E-value analysis suggested that a considerable amount of unaccounted confounding would be necessary to invalidate the observed associations.ConclusionsThe ROX index is inversely associated with mortality in critically ill patients with COPD, with higher values indicating better prognosis. It may serve as a simple, non-invasive, and valuable tool for early risk stratification in the ICU setting.