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Ionosonde data and crustal earthquakes with magnitude M ≥ 6.0 observed in Greece during the 2003–2015 period were examined to check if the relationships obtained earlier between precursory ionospheric anomalies and earthquakes in Japan and central Italy are also valid for Greek earthquakes. The ionospheric anomalies are identified on the observed variations of the sporadic E-layer parameters (h′Es, foEs) and foF2 at the ionospheric station of Athens. The corresponding empirical relationships between the seismo-ionospheric disturbances and the earthquake magnitude and the epicentral distance are obtained and found to be similar to those previously published for other case studies. The large lead times found for the ionospheric anomalies occurrence may confirm a rather long earthquake preparation period. The possibility of using the relationships obtained for earthquake prediction is finally discussed.