Large intraplate intermediate-depth (IID) events are the most destructive to Chilean structures and they occurred throughout the country. Cities located above the hypocenters of these large earthquakes have been completely destroyed. In recent years, only small- and moderate-magnitude IID events have been reported below Santiago, the most populated Chilean city; however, the occurrence of large-magnitude IID events cannot be ruled out. In this study, we investigated the strong-ground motion generated by large-magnitude earthquakes occurring below the Santiago metropolitan region. We used a stochastic methodology to simulate synthetic records, considering IID events of magnitude Mw 7.8. To validate this method, we simulated intermediate-depth events of magnitudes Mw ∼5-6 that occurred near Santiago. We further calibrate our results by reproducing the strong-ground motion data recorded during the 2005 Tarapacá Mw 7.8 Northern Chile IID earthquake. We observe that in some areas of the Santiago Basin, high PGA values can reach values close to 1 g, in which, in addition to directivity effects and takeoff angles, the rupture distances (∼100 km) and soil type (C) play a key role in amplifying strong-ground motion. Finally, our findings highlight the importance of reproducing high-frequency time histories as a proxy to re-evaluate the seismic hazard due to large IID earthquakes.