With the aggravation of the aging of the world population, frailty has become one of the common complications in elderly people. Its diagnosis is not objective, the pathogenesis is not clear, and interventions are not sound, thus intensifying the problem. Furthermore, frailty is closely associated with the occurrence and poor prognosis of coronary atherosclerotic heart disease. Moreover, few studies report on the prevalence of frailty in elderly patients with the chronic coronary syndrome (CCS).We aimed to investigate the prevalence of frailty in elderly patients with CCS. We analyzed the correlation between the blood serum levels of interleukin-6 (IL-6), albumin (Alb), and 25-hydroxyvitamin D (25(OH)D) with frailty in elderly patients with CCS. We have also provided recommendations for helping the objective diagnosis as well as proposed new intervention methods in the future.Two hundred eight-eight inpatients (≥60 years) with the chronic coronary syndrome were recruited at the Department of Geriatrics, the First People's Hospital of Yunnan Province, China. General information and laboratory examination data were collected. The comprehensive geriatric assessment was conducted via an internet-based platform of the Comprehensive Geriatric Assessment (inpatient version) developed by us, among which frailty was assessed by the Chinese version of Fried Frailty Phenotype, a component of the assessment scale.Among the total number of old patients with CCS, 87 (30.2%) had no frailty, 93 (32.3%) had early frailty, and 108 (37.5%) had frailty. According to the multivariate logistic regression analysis, after adjusting for confounding factors, IL-6 (OR = 1.066, 95% CI 1.012-1.127), Alb (OR = 0.740, 95% CI 0.560-0.978), and 25(OH)D (OR = 0.798, 95% CI 0.670-0.949) were independently associated with frailty in the three groups of models.IL-6 proved to be a risk factor for frailty in elderly patients with CCS, while Alb and 25(OH)D were protective factors, which make the potential targets for predicting and intervening frailty in elderly patients with CCS.© 2022 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.