Abstract Background Management of elderly patients with acute myocardial infarction (AMI) is challenging due to lack of knowledge about the link between fragility, outcomes and interventional procedures. Aims The aim of this study was to establish the prognostic role of the Multidimensional Prognostic Index (MPI) in elderly with AMI. Methods A total of 241 patients ≥ 65 years old with AMI were continuously enrolled in this prospective study and divided into three groups according to the MPI score. The primary endpoint was 30-day mortality. Secondary endpoints were 6-month mortality and rate of adverse events. Results In-hospital overall mortality rate was higher in MPI-3 (p = 0.009). Patients of MPI-3 had a significantly higher mortality rate regarding the primary endpoint with 30-day survival of 78.9%, compared to 97.4% and 97.2%, in MPI-1, MPI-2 (p < 0.001), respectively. The survival rate progressively decreased in the three MPI classes of risk with a 6-month survival of 96.5%, 96.3%, 73.7% in groups MPI-1, MPI-2, and MPI-3 (p < 0.001). Longer length of in-hospital stay was observed in MPI-3 group. In-hospital complications were more frequent in higher MPI score. Discussion Our findings are in agreement with the results of other studies that evaluated the risk of in-hospital complications and mortality in older patients. In our “real-world” population of elderly hospitalized for AMI we observed poorer outcomes in patients belonged to higher MPI groups. Conclusions In the setting of AMI, MPI may be very useful in the daily clinical practice to manage older patients and predict the risk of in-hospital and follow-up complications.