The aim of this study was to evaluate the combined prognostic value of calf circumference (CC) and serum albumin on mortality in patients with cancer cachexia aged ≥65 years.This multicenter cohort study involved 5322 older patients in hospital with cancer cachexia. The combined indicator of CC and albumin was defined as the calf circumference-albumin (CCA) index. Harrell's C index, a time-dependent receiver operating characteristic curve analysis, was used to assess the prognostic performance of the CCA index and other indices. The optimal thresholds method was used to determine the cutoff values of CC and albumin, and the association between the CCA index and all-cause mortality was assessed using Kaplan-Meier analysis and Cox proportional hazard regression models.A total of 3875 men and 1447 women with a mean age of 72.0 years (range: 68.0-78.0 years) and a mean follow-up time of 55.0 months (range: 25.0-85.0 months) were included in the study. A total of 1269 patients were classified into the low CCA index group (0 score) by the optimal thresholds method. In the overall population, the CCA index showed better differentiating power at predicting mortality in older patients with cancer cachexia compared with CC or albumin alone (C index = 0.639; 95% CI: 0.612-0.666; P < 0.05). The time-dependent receiver operating characteristic curve showed that the CCA index had the highest prognostic value of all the measures studied (P < 0.05). In the overall population, male and female patients with a high CCA index (2 score) showed better performance than those with a low CCA index (0 or 1 score).The CCA index could significantly predict the mortality of older patients with cancer cachexia, which might provide renewed assistance for future clinical management.Copyright © 2024 Elsevier Inc. All rights reserved.