A multidimensional impairment may influence the clinical outcome of acute diseases in older patients. The aim of the current study was to evaluate whether a Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment (CGA) predicts short- and long-term all-cause mortality in older patients hospitalized for transient ischemic attack (TIA). In this prospective study with 1-year follow-up, 654 patients aged 65 and older with a diagnosis of TIA according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM 435.x) were enrolled. A standardized CGA that included information on functional (activities of daily living, ADL, and Instrumental ADL), cognitive status (Short Portable Mental Status Questionnaire), nutrition (Mini Nutritional Assessment), risk of pressure sores (Exton-Smith Scale), comorbidities (Cumulative Illness Rating Scale), medications and co-habitation status was used to calculate the MPI for mortality using a previously validated algorithm. Higher MPI values were significantly associated with higher 1-month all-cause mortality (incidence rates: MPI-1 low risk = 0.32%, MPI-2 moderate risk = 5.36%, MPI-3 high risk = 10.42%; p < 0.001), 6-month all-cause mortality (MPI-1 = 1.95%, MPI-2 = 9.77%, MPI-3 = 27.22%; p < 0.001) and 12-month all-cause mortality (MPI-1 = 5.19%, MPI-2 = 16.47%, MPI-3 = 44.32%; p < 0.001). Age- and gender-adjusted Cox regression analyses demonstrated that MPI was a significant predictor of all-cause mortality. MPI showed a significant high discriminatory power with an area under the receiver operating characteristics (ROC) curve of 0.819, 95% CI = 0.749-0.888 for 1-month mortality, 0.799, 95% CI = 0.738-0.861 for 6-month mortality and 0.770, 95% CI = 0.716-0.824 for 12-month mortality. The MPI, calculated from information collected in a standardized CGA, appeared to be effective in estimating short- and long-term all-cause mortality in older patients hospitalized for TIA.