BackgroundFrailty is a marker of poor prognosis in older adults with hematologic malignancies and contributes to the severe vulnerability of the aging population to adverse health outcomes. This study aimed to determine the association between frailty and outcomes in hospitalized patients with chronic myeloid leukemia (CML).MethodsThe International Classification of Diseases (ICD-10) identified data on hospitalized patients 20 years or older admitted with CML between 2016 and 2018 in the US National Inpatient Sample (NIS) database. The cohort was further divided into groups of patients with or without frailty. Logistic regression analysis was performed to determine associations between study variables and clinical outcomes. A stratified analysis of the association between frailty and in-hospital mortality by age group was also performed.ResultsA total of 13,849 hospitalized patients with CML were included, 49.6% of whom had frailty. The mean age of the patients was 65.1 years, and 7,619 (56.2%) of them were male. Frailty was associated with nearly 4 times the risk of in-hospital mortality, 3 times the risk of unfavorable discharge, 3 times the risk of prolonged LOS,, and significantly more in total hospital costs. In addition, frailty was associated with a significantly increased risk of in-hospital mortality in all age subgroups (< 40 years, 40–59 years, and > 60 years) compared with no frailty.ConclusionsFrailty strongly predicts poor clinical outcomes in US patients with CML.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12877-023-03962-7.