Background: Increased red cell distribution width (RDW) reflects a severe dysregulation of erythrocyte homeostasis and has been linked to poor prognosis in various clinical hematological and non-hematological conditions. Additionally, the RDW to platelet ratio (RPR) is a novel inflammatory index and has gained considerable attention as a prognostic marker on critically ill patients. Aim: Evaluation of the prognostic usefulness of RDW and its derived ratio (RPR) at the time of admission in patients of intensive care units (ICU). Patients and methods: This prospective cohort study was conducted on 42 patients admitted to the medical ICU of the internal Medicine Department, at Zagazig University Hospitals, during the period from October 2022 to March 2023. The baseline RDW and RPR were measured and patients were followed during the hospital stay then divided into 2 groups according to the survival outcome and proper statistical analyses were used for the detection of the prognostic relevance of the studied parameters. Results: The optimal cutoff of RDW for prediction of mortality was 16.25 (p<0.05), while the RPR was 0.0723 and Higher RDW was significantly associated with lower overall survival (p= 0.025), and on multivariate analysis was the only factor significantly associated with mortality (p= 0.002), whereas the RPR did not affect the patient outcome. Conclusion: RDW is an affordable CBC-based parameter that can be used as an independent predictor of mortality in critically ill ICU patients.