The aim of this study was to provide a contribution to seismic hazard assessment of the Salento Peninsula (Apulia, southern Italy). It is well known that this area was struck by the February 20, 1743, earthquake (I 0 = IX and M w = 7.1), the strongest seismic event of Salento, that caused the most severe damage in the towns of Nardò (Lecce) and Francavilla Fontana (Brindisi), in the Ionian Islands (Greece) and in the western coast of Albania. It was also widely felt in the western coast of Greece, in Malta Islands, in southern Italy and in some localities of central and northern Italy. Moreover, the area of the Salento Peninsula has also been hit by several low-energy and a few high-energy earthquakes over the last centuries; the instrumental recent seismicity is mainly concentrated in the western sector of the peninsula and in the Otranto Channel. The Salento area has also experienced destructive seismicity of neighboring regions in Italy (the Gargano Promontory in northern Apulia, the Southern Apennines chain, the Calabrian Arc) and in the Balkan Peninsula (Greece and Albania). Accordingly, a critical analysis of several documentary and historical sources, as well as of the geologic–geomorphologic ground effects due to the strong 1743 Salento earthquake, has been carried out by the authors in this paper; the final purpose has been to re-evaluate the 1743 MCS macroseismic intensities and to provide a list of newly classified localities according to the ESI-07 scale on the base of recognized Earthquake Environmental Effects. The result is a quite different damage scenario due to this earthquake that could raise the seismic potential currently recognized for the Salento area, and consequently upgrade the seismic hazard classification of the Salento. Indeed it is important to remind that currently, despite the intense earthquake activity recorded not only in the Otranto Channel, but especially in Greece and Albania, this area is classified in the least dangerous category of the Seismic Classification of the Italian territory (IV category).