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Objective: Frailty is a syndrome that predisposes older individuals to adverse health outcomes, such as disability, dependence, falls, hospitalization, post-operative complications, and poor health in general. This study aimed to identify factors associated with frailty in older people with chronic diseases in Colombia. Methods: A cross-sectional study was conducted with a nonprobabilistic sample of 230 older people (aged ⩾ 60 years) from four Colombian cities. Frailty was based on Fried’s phenotype (frail defined as having ⩾3 criteria). Comorbidities were classified based on Charlson’s Comorbidity Index and key questionnaires for activities of daily living (ADLs) were evaluated. Results: Most were female (57.8%) with a mean ± SD age of 71.9 ± 8 years. Among them, 27.4% were frail and 58.7% were prefrail. Female gender, age ⩾ 75 years, low educational and socioeconomic level, dependence on ADLs, and cognitive impairment were associated with higher odds of prefrailty/frailty. Conclusions: Prefrailty and frailty are common among older people with chronic diseases in Colombia. This syndrome is associated with social and health-related conditions, which should be addressed when providing care for these patients.