Introduction and Objectives: Kidney transplant (KT) recipients who experience graft failure and return to dialysis face a higher risk of adverse outcomes. This study aimed to identify risk factors for hospitalization and mortality two years post-graft failure. Materials and Methods: We conducted a retrospective cohort study of end-stage kidney disease patients who initiated hemodialysis following graft failure between January 2019 and December 2020. The Clinical Frailty Scale (CFS) and the Charlson Comorbidity Index (CCI) were assessed for each patient at the time of graft loss. The primary outcomes were hospitalization and all-cause mortality over a two-year follow-up period. Results: A total of 107 patients were included, with a mean age of 55 years and a mean graft survival of 134 months. The two-year hospitalization rate was 37.4%, with lower residual diuresis and higher CFS identified as independent risk factors. The two-year mortality rate was 16.8%. A multivariate regression model, explaining 82% of the variance, confirmed that higher CCI, higher CFS, and lower residual diuresis significantly increased mortality risk. A CCI cut-off of ≥ 8 (AUC 0.95) further stratified patients at elevated mortality risk. Immunological and transplant-related variables did not influence mortality or hospitalization risk. Conclusions: In this cohort, frailty defined by CFS was associated with hospitalization and mortality, while comorbidity burden evaluated by CCI was strongly related to mortality. These tools may help personalize the care of patients with a failing graft.