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Purpose: To evaluate different registration methods, setup margins and number of corrections for CBCT-based position verification for oesophageal cancer and to evaluate anatomical changes during the course of radiotherapy treatment., Methods: From 50 patients, 440 CBCT-scans were registered automatically using a soft tissue or bone registration algorithm and compared to the clinical match. Moreover, relevant anatomical changes were monitored. A sub-analysis was performed to evaluate if tumour location influenced setup variations. Margin calculation was performed and the number of setup corrections was estimated. Results were compared to a patient group previously treated with MV-EPID based position verification., Results: CBCT-based setup variations were smaller than EPID-based setup variations, resulting in smaller setup margins of 5.9 mm (RL), 7.5 mm (CC) and 4.7 mm (AP) versus 6.0 mm, 7.8 mm and 5.5 mm, respectively. A reduction in average number of setup corrections per patient was found from 0.75 to 0.36. From all automatically registered CBCT-scans, a clipbox around PTV and vertebras combined with soft tissue registration resulted in the smallest setup margins of 5.9 mm (RL), 7.7 mm (CC), 4.8 mm (AP) and smallest average number of corrections of 0.38. For distally located tumours, a setup margin of 7.7 mm (CC) was required compared to 5.6 mm for proximal tumours. Reduction of GTV volume, heart volume and change in diaphragm position were observed in 16, 10 and 15 patients, respectively., Conclusions: CBCT-based set-up variations are smaller than EPID-based variations and vary according to tumour location. When using kV-CBCT a large variety of anatomical changes is revealed, which cannot be observed with MV-EPID., (© 2017 The Authors. Published by Elsevier Ireland Ltd on behalf of European Society for Radiotherapy & Oncology.)