In a recent multicenter study, discrepancies between PET/CT-measured activity and vendor-calibrated activity for ⁹⁰ Y glass and resin microspheres were found. In the present work, the origin of these discrepancies was investigated by Monte Carlo (MC) simulations. Methods: Three vial configurations, containing ⁹⁰ Y-chloride, ⁹⁰ Y-labeled glass microspheres, and ⁹⁰ Y-labeled resin microspheres, were modeled with GAMOS, and the electric signal generated in an activity meter was simulated. Energy deposition was scored in the activity meter-active regions and converted into electric current per unit activity. Internal bremsstrahlung (IB) photons, always accompanying β-decay, were simulated in addition to ⁹⁰ Y decays. The electric current per source activity obtained for ⁹⁰ Y glass and resin microspheres, I _glass and I _resin , was compared in terms of relative percentage difference with that of ⁹⁰ Y-chloride ([Formula: see text] and [Formula: see text]) and each other (δ). The findings of this work were compared with the ones obtained through PET measurements in the multicenter study. Results: With the inclusion of IB photons as primary particles in MC simulations, the [Formula: see text] and [Formula: see text] results were 24.6% ± 3.9% and -15.0% ± 2.2%, respectively, whereas δ was 46.5% ± 1.9%, in very good agreement with the values reported in the multicenter study. Conclusion: The MC simulations performed in this study indicate that the discrepancies recently found between PET/CT-measured activity and vendor-calibrated activity for ⁹⁰ Y glass and resin microspheres can be attributed to differences in the geometry of the respective commercial vials and to the metrologic approach adopted for activity meter calibration with a ⁹⁰ Y-chloride liquid source. Furthermore, IB photons were shown to play a relevant role in determining the electric current in the activity meter.