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Cardiorenal syndrome (CRS) is a complex condition defined by bidirectional interactions between the heart and kidneys and is associated with high morbidity and mortality. Biological aging measures, including PhenoAge, the Klemera–Doubal method (KDM), and phenotypic age acceleration (PAA), have been associated with mortality in both the general population and individuals with chronic diseases. Their prognostic relevance in CRS remains unclear. This study evaluated the associations of these measures with all-cause, cardiovascular disease (CVD), and non-CVD mortality in U.S. adults with CRS. We analyzed data from 1,195 CRS participants enrolled in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. Biological aging was assessed using PhenoAge and KDM. The residuals from the regression of phenotypic age on chronological age (AAR) were used to determine PAA status. Participants were classified as having PAA or not having PAA based on the residuals. Outcomes included all-cause, CVD, and non-CVD mortality. Survey-weighted Cox proportional hazards models were used to estimate associations. Subgroup analyses were conducted to assess effect modification, and sensitivity analyses to evaluate consistency. During a median follow-up of 7.17 years, 630 deaths were documented, including 234 from CVD and 396 from non-CVD causes. The baseline characteristics of the study population are summarized as follows: the mean age of participants was 73.5 ± 8.7 years. The mean biological age, as assessed by PhenoAge, was 82.7 ± 12.4 years, while the mean biological age based on the KDM was 81.6 ± 21.7 years. The mean AAR was − 0.1 ± 10.9 years. Regarding PAA, 62.5% of participants (710 individuals) did not exhibit PAA, while 37.5% (485 individuals) had positive PAA values. Higher PhenoAge and KDM values were significantly associated with increased risks of all-cause, CVD, and non-CVD mortality after adjustment for confounders. Each unit increase in PhenoAge was associated with a 4% higher risk of all-cause mortality (HR: 1.04; 95% CI 1.02, 1.05), and each unit increase in KDM was associated with a 2% higher risk (HR: 1.02; 95% CI 1.01, 1.02). PAA was associated with over a twofold higher risk of all-cause mortality (HR: 2.20; 95% CI 1.65, 2.93) and with increased risks of both CVD (HR: 2.49; 95% CI 1.64, 3.79) and non-CVD mortality (HR: 1.92; 95% CI 1.35, 2.73). Smoking and diabetes modified the associations between PhenoAge and mortality, and diabetes further modified the association between PAA and mortality. Biological aging measures and PAA were independently associated with mortality in U.S. adults with CRS, over and above chronological age and established risk factors. Incorporating these measures into clinical assessment may improve risk stratification and support more tailored management strategies in this high-risk population.