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This article presents a revised voxel S values (VSVs) approach for dosimetry in targeted radiotherapy, allowing dose calculation for any voxel size and shape of a given SPECT or PET dataset. This approach represents an update to the methodology presented in MIRD pamphlet no. 17. Methods: VSVs were generated in soft tissue with a fine spatial sampling using the Monte Carlo (MC) code MCNPX for particle emissions of 9 radionuclides: ^sup 18^F, ^sup 90^Y, ^sup 99m^Tc, ^sup 111^In, ^sup 123^I, ^sup 131^I, ^sup 177^Lu, ^sup 186^Re, and ^sup 201^TI. A specific resampling algorithm was developed to compute VSVs for desired voxel dimensions. The dose calculation was performed by convolution via a fast Hartley transform. The fine VSVs were calculated for cubic voxels of 0.5 mm for electrons and 1.0 mm for photons. Validation studies were done for ^sup 90^Y and ^sup 131^I VSV sets by comparing the revised VSV approach to direct MC simulations. The first comparison included 20 spheres with different voxel sizes (3.8-7.7 mm) and radii (4-64 voxels) and the second comparison a hepatic tumor with cubic voxels of 3.8 mm. MC simulations were done with MCNPX for both. The third comparison was performed on 2 clinical patients with the 3D-RD (3-Dimensional Radiobiologic Dosimetry) software using the EGSnrc (Electron Gamma Shower National Research Council Canada)-based MC implementation, assuming a homogeneous tissue-density distribution. Results: For the sphere model study, the mean relative difference in the average absorbed dose was 0.20% ± 0.41% for ^sup 90^Y and -0.36% ± 0.51% for ^sup 131^I (n = 20). For the hepatic tumor, the difference in the average absorbed dose to tumor was 0.33% for ^sup 90^Y and -0.61 % for ^sup 131^I and the difference in average absorbed dose to the liver was 0.25% for ^sup 90^Y and -1.35% for ^sup 131^I. The comparison with the 3D-RD software showed an average voxel-to-voxel dose ratio between 0.991 and 0.996. The calculation time was below 10 s with the VSV approach and 50 and 15 h with 3D-RD for the 2 clinical patients. Conclusion: This new VSV approach enables the calculation of absorbed dose based on a SPECT or PET cumulated activity map, with good agreement with direct MC methods, in a faster and more clinically compatible manner.