OBJECTIVE Radiotherapy (RT) based on magentic resonance imaging (MRI) only is currently used clinically in the pelvis. A synthetic computed tomography (sCT) is needed for dose planning. Here, we investigate the accuracy of cone beam CT (CBCT) based MRI-only image guided RT (IGRT) and sCT image quality. METHODS CT, MRI and CBCT scans of ten prostate cancer patients were included. The MRI was converted to a sCT using a multi-atlas approach. The sCT, CT and MR images were auto-matched with the CBCT on the bony anatomy. Paired sCT-CT and sCT-CBCT data were created. CT numbers were converted to relative electron (RED) and mass densities (DES) using a standard calibration curve for the CT and sCT. For the CBCT RED/DES conversion, a phantom and paired CT-CBCT population based calibration curve was used. For the latter, the CBCT numbers were averaged in 100 HU bins and the known RED/DES of the CT were assigned. The paired sCT-CT and sCT-CBCT data were averaged in bins of 10 HU or 0.01 RED/DES. The median absolute error (MeAE) between the sCT-CT and sCT-CBCT bins was calculated. Wilcoxon rank-sum tests were carried out for the IGRT and MeAE study. RESULTS The mean sCT or MR IGRT difference from CT was ≤ 2 mm but significant differences were observed. A CBCT HU or phantom-based RED/DES MeAE did not estimate the sCT quality similar to a CT based MeAE but the CBCT population-based RED/DES MeAE did. CONCLUSIONS MRI-only CBCT-based IGRT seems feasible but caution is advised. A MeAE around 0.1 DES could call for sCT quality inspection.