Background Frailty, demographic and clinical variables linked to incident diseases (e.g., dehydration, inflammation) contribute to poor outcomes in older patients acutely hospitalized. Their predictivity on short-, intermediate- and long-term mortality in a comprehensive model has been scarcely investigated. Aims To test the performance of a predictive tool considering frailty and inflammation as well as age, sex and impaired hydration status on 1-year mortality in acutely admitted older patients. Methods Retrospective observational study including 529 medical patients (age 84.6 ± 7.3 years). At hospital admission, frailty was assessed by the Multidimensional Prognostic Index (MPI). The Glasgow Prognostic Score (GPS) was used to grade systemic inflammation. Serum osmolarity was calculated to assess hydration. Results After adjusting for age, sex, GPS and osmolarity, the severe-risk MPI was a strong predictor for 1-year mortality (OR 4.133; 95% CI 2.273–7.516; p < 0.001). Age > 85 years, male sex, GPS-2 and serum osmolarity > 300 mOsm/L were independent predictors of mortality in the same multivariable model. The MPI alone showed a moderate discrimination power (AUC 0.678; 95% CI 0.628–0.729; p < 0.001) on 1-year mortality, which increased by 12.5% after the addition of the above predictors in the fully adjusted regression model (AUC 0.763; 95% CI 0.719–0.807; p < 0.001). The severe-risk MPI adjusted for the same factors was also an independent predictor of mortality after 60 and 180 days since hospital admission. Discussion Inflammation and impaired hydration are potentially modifiable risk factors for severe outcomes in older acutely hospitalized patients. A model combining GPS, age, gender, and plasma osmolarity improved the accuracy of MPI at admission in predicting long-term mortality.