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An effective mitigation of seismic risk in Italy can hardly be obtained without a tentative recognition of few priority zones, where the limited resources available in the short term can be concentrated. A reliable recognition of the zones where the probability of major earthquakes is highest must be carried out by a deterministic approach, exploiting the profound knowledge acquired about the present seismotectonic context in the zones involved. Some years ago, this kind of procedure led us to identify the central-northern Apennines (i.e. the zone hit by the recent major earthquakes, 2016 and 2017) as the Italian area most prone to next strong shocks. The reliability of the methodology here proposed is also supported by the fact that the implications of the adopted tectonic setting can provide plausible and coherent explanations for the spatio-temporal distribution of major earthquakes in the central Mediterranean area in the last six centuries.