The matrix, IJK_TO_DICOM_REAL, is not taken into account normally in every AFNI command except for the special options for 3dWarp and 3drefit and the matrix information in 3dinfo. Opening two controllers in the AFNI GUI and locking the controllers together will show the closest corresponding voxel center coordinates at the crosshair location. Most AFNI commands require all input datasets to be on the same grid, so that will usually require 3dresample, 3dfractionize, 3dWarp or 3dAllineate to resample the datasets. Those output datasets will share the same origin and voxel size. Again you can verify this with the AFNI GUI and 3dinfo.
There is a caveat of dealing with NIFTI files. In the case of writing NIFTI files, the s-form matrix is written to the dataset using the IJK_TO_DICOM_REAL matrix. Reading in NIFTI files, the s-form or q-form matrices determine the IJK_TO_DICOM_REAL matrix and the cardinal equivalent matrix unless the IJK_TO_DICOM_REAL matrix already exists as a special AFNI extension within the NIFTI file. This presents the possibility of conflicting information between the q or s-forms and the IJK_TO_DICOM_REAL matrix. You can search the message board for recent issues reading NIFTI files.