A feasibility study of a novel PET-based molecular image guided radiation therapy (m-IGRT) system was conducted by comparing PET-based digitally reconstructed planar image (PDRI) registration with radiographic registration. We selected a pair of opposing parallel-plane PET systems for the practical implementation of this system. Planar images along the in-plane and cross-plane directions were reconstructed from the parallel-plane PET data. The in-plane and cross-plane FWHM of the profile of 2 mm diameter sources was approximately 1.8 and 8.1 mm, respectively. Therefore, only the reconstructed in-plane image from the parallel-plane PET data was used in the PDRI registration. In the image registration, five different sizes of (18)F cylindrical sources (diameter: 8, 12, 16, 24, 32 mm) were used to determine setup errors. The data acquisition times were 1, 3 and 5 min. Image registration was performed by five observers to determine the setup errors from PDRI registration and radiographic registration. The majority of the mean registration errors obtained from the PDRI registration were not significantly different from those obtained from the radiographic registration. Acquisition time did not appear to result in significant differences in the mean registration error. The mean registration error for the PDRI registration was found to be 0.93 ± 0.33 mm. This is not statistically different from the radiographic registration which had a mean registration error of 0.92 ± 0.27 mm. Our results suggest that m-IGRT image registration using PET-based reconstructed planar images along the in-plane direction is feasible for clinical use if PDRI registration is performed at two orthogonal gantry angles.