The present study is a comparative investigation of the luminescence properties of (Lu,Y)2SiO5:Ce (LYSO:Ce), Lu2SiO5:Ce (LSO:Ce), Gd2SiO5:Ce (GSO:Ce) and (Bi4Ge3O12) BGO single crystal scintillators under medical X-ray excitation. All scintillating crystals have dimensions of 10 × 10 × 10 mm3 are non-hygroscopic exhibiting high radiation absorption efficiency in the energy range used in medical imaging applications. The comparative investigation was performed by determining the absolute luminescence efficiency (emitted light flux over incident X-ray exposure) in X-ray energies employed in general X-ray imaging (40–140 kV) and in mammographic X-ray imaging (22–49 kV). Additionally, light emission spectra of crystals at various X-ray energies were measured, in order to determine the spectral compatibility to optical photon detectors incorporated in medical imaging systems and the overall efficiency (effective efficiency) of a scintillator–optical detector combination. The light emission performance of LYSO:Ce and LSO:Ce scintillators studied was found very high for X-ray imaging.