BackgroundThe Clinical Frailty Scale (CFS) is a well-established tool that has been widely employed to assess patients' frailty status and to predict clinical outcomes in the acute phase of a disease, but more information is needed to define the implications that this tool have when dealing with Non-Communicable Diseases (NCDs).MethodsAn electronic literature search was performed on PubMed, Scopus, EMBASE, Web of Science, and EBSCO databases to identify studies employing the CFS to assess frailty in patients with NCDs.FindingsAfter database searching, article suitability evaluation, and studies' quality assessment, 43 studies were included in the systematic review. Researches were conducted mostly in Japan (37.5%), and half of the studies were focused on cardiovascular diseases (46.42%), followed by cancer (25.00%), and diabetes (10.71%). Simplicity (39.29%), efficacy (37.5%), and rapidity (16.07%) were the CFS characteristics mostly appreciated by the authors of the studies. The CFS-related results indicated that its scores were associated with patients' clinical outcomes (33.92%), with the presence of the disease (12.5%) and, with clinical decision making (10.71%). Furthermore, CFS resulted as a predictor of life expectancy in 23 studies (41.07%), clinical outcomes in 12 studies (21.43%), and hospital admissions/readmissions in 6 studies (10.71%).DiscussionCFS was found to be a well-established and useful tool to assess frailty in NCDs, too. It resulted to be related to the most important disease-related clinical characteristics and, thus, it should be always considered as an important step in the multidisciplinary evaluation of frail and chronic patients.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.asp? PROSPERO 2021, ID: CRD42021224214.