PURPOSE: This cost analysis aimed to quantify the cost of IGRT in relation to IGRT frequency and modality with Cone Beam Computed Tomography (CBCT) or orthogonal electronic portal imaging with fiducial markers (EPI-FM). MATERIAL AND METHODS: Patients undergoing IGRT for localized prostate cancer were randomized into two prostate control frequencies (daily or weekly). Costs were calculated based on the micro-costing results according to hospitals' perspectives (in Euros, 2009) and the time horizon was radiation therapy. RESULTS: A total of 208 patients were enrolled in seven French cancer centers. A total of 6865 fractions were individually analyzed. The mean total treatment fraction duration was 21.0 min for daily CBCT and 18.3 min for daily EPI-FM. Increasing the control frequency from weekly to daily increased the mean treatment fraction duration by 7.3 min (+53%) for CBCT and 1.7 min (+10%) for EPI-FM (p ≤ 0.01). The mean additional cost per patient of daily controls compared with weekly controls was €679 and €187 for CBCT and EPI-FM, respectively (p