Background: Accurate reconstruction and quantification in post-therapy SPECT/CT imaging of 166Ho microspheres for hepatic malignancies is crucial for treatment evaluation. This present study aimed to explore the impact of the OSEM reconstruction parameters on SPECT/CT image features for dose distribution determination, using Hybrid Recon™ (Hermes Medical Solutions AB) and full Monte Carlo (MC) collimator modeling. Methods: Image quality and activity quantification were evaluated using Jaszczak and PTW SPECT/PET body phantoms. Siemens Symbia Intevo Bold and Symbia Pro.specta camera models were used for imaging. Datasets were reconstructed using OSEM (varying number of iterations) with and without full MC collimator modeling. Contrast recovery coefficients (QH), coefficients of variation (CV), calibration factors (CF) and activity recovery coefficients (ARC) were calculated and used to evaluate image quality and activity quantification. Results: The reconstruction method that provided the higher QH and ARCs in both studied systems/phantoms was the one applying 5 iterations and 15 subsets, incorporating full Monte Carlo collimator modeling. CF were (14.5±0.6) cps/MBq and (15.4±0.5) cps/MBq for the Siemens Symbia Intevo Bold and Symbia Pro.specta, respectively, corresponding to Jaszczak and PTW SPECT/PET body phantoms. The two analytical approaches used to fit the ARCs data confirmed the expected activity underestimation in small volumes due to partial volume effect (PVE) and the validity of the results in two different scanners and phantoms. Conclusions: For post-SIRT 166Ho SPECT/CT imaging, OSEM (5 iterations, 15 subsets) with full Monte Carlo collimator modeling provided superior quantification results. The determination of CF and ARC is vital for accurate quantification of 166Ho and should be always considered.