The purpose of the current study was to investigate the predictive properties of five definitions of a frailty risk score (FRS) and three comorbidity indices using data from electronic health records (EHRs) of hospitalized adults aged ≥50 years for 3-day, 7-day, and 30-day readmission, and to identify an optimal model for a FRS and comorbidity combination. Retrospective analysis of the EHR dataset was performed, and multivariable logistic regression and area under the curve (AUC) were used to examine readmission for frailty and comorbidity. The sample (N = 55,778) was mostly female (53%), non-Hispanic White (73%), married (53%), and on Medicare (55%). Mean FRSs ranged from 1.3 (SD = 1.5) to 4.3 (SD = 2.1). FRS and comorbidity were independently associated with readmission. Predictive accuracy for FRS and comorbidity combinations ranged from AUC of 0.75 to 0.77 (30-day readmission) to 0.84 to 0.85 (3-day readmission). FRS and comorbidity combinations performed similarly well, whereas comorbidity was always independently associated with readmission. FRS measures were more associated with 30-day readmission than 7-day and 3-day readmission. [Research in Gerontological Nursing, 14(2), 91-103.].