BackgroundBiological age is increasingly being recognized as an important predictor of health but its utility in acute care setting remains uncertain. ObjectiveWe assessed whether biological age on intensive care unit (ICU) admission can predict unplanned ICU readmission during the same hospitalization. MethodsThe Levine PhenoAge model based on biomarkers of DNA methylation was used to determine each patient's biological age. The difference between PhenoAge and chronological age was indexed to the local context by regressing PhenoAge on chronological age using linear regression. A positive residual implied one's biological age was older than the corresponding chronological age compared to other patients — defined as PhenoAgeAccel. ResultsOf the 2950 patients included, 153 (5.2%) had unplanned ICU readmission. Chronological age, Acute Physiology and Chronic Health Evaluation II score, the use of mechanical ventilation, vasopressor, or renal replacement therapy were not significantly different between those with and without readmission. PhenoAgeAccel was, however, more common among those who had unplanned ICU readmission (52% vs 43%, p =0.031). Quantitatively, the degree of phenotypical age above chronological age exhibited a ‘dose-related’ relationship with the risk of readmission (odds ratio 1.12, 95% confidence interval 1.01-1.24; p=0.040) after adjusting for chronological age, comorbidities, and severity of acute illness in the index (first) ICU admission. ConclusionBiological age was predictive of unplanned ICU readmission during the same hospitalization.