The 3D wave‐propagation characteristics of the 4 July 1978 aftershock (M 5.1) of the 20 June 1978 strong mainshock (M 6.5) that struck the city of Thessaloniki are studied using a 3D finite‐difference approach. Synthetics are estimated for a dense grid of receivers and compared with available accelerograms from soft‐soil sites in the city of Thessaloniki, exhibiting a good agreement both in time and frequency domain for the frequency band studied (0.7–3 Hz). Moreover, the spatial distribution of various measures of ground motion (peak values, spectral values) is used for the quantitative study of site effects in the broader city area. Comparisons show that the coastal zone, including the city harbor and large areas of the eastern parts of the city, exhibit high values of ground motion (and significant site amplifications), in good qualitative correlation with the observed damage distribution of the mainshock of the 1978 seismic sequence. Finally, the 3D synthetics are compared with available 2D simulations, as well as amplifications derived from macroseismic information for three typical cross sections spanning the urban area of the city. The comparisons confirm the strong spatial variability of ground motion throughout the Thessaloniki area, as well as the superiority of 3D modeling of actual recordings against previous modeling attempts. These results verify the practical usefulness of 3D wave‐propagation tools for hazard mitigation, especially of specific target events, in complex geometry sedimentary basins such as the Thessaloniki area.