Background and study aimsEndoscopy Ultra-Sound (EUS)-guided fiducial marker placement in patients with esophageal or rectal cancer who have been referred for radiation therapy lacks data regarding its feasibility and safety. The aim of this study was to assess the success rate of EUS-guided fiducial marker placement in these indications. Patients and methodsThis prospective multicenter study enrolled patients with rectal or esophageal tumor, who were treated between March 2017 and June 2021. The primary endpoint was the success of fiducial markers placement under EUS guidance utilizing the preloaded 22-gauge EchoTip Ultra Fiducial needle® (Cook Medical, Limerick, Ireland), defined by the ability to release fiducials at least at proximal and distal ends of the tumor. The secondary endpoints were the adverse events, length of procedure, and remaining fiducial markers throughout radiation therapy. ResultsA total of 33 patients were included in this study, with a mean age of 64.2 years ±11.3, and 66.7% of males. Twenty patients had rectal adenocarcinoma, and 13 had esophageal malignancies. The success rate of fiducial markers placement was 93.9%. Markers could only be released at the proximal end of the tumor in two cases. The average procedure time (±SD) was 12.5 min (±4.8). The number of fiducial markers placed for each patient was 3.8 (±0.5). No adverse event was reported. At the end of radiotherapy, markers were still visible on imaging in all patients. ConclusionThis prospective multicenter study highlights the safety and high success of the placement of fiducial markers under EUS, for rectal and esophageal tumors, without adverse event, and with a short procedure time. Fiducial markers remain in place over time during radiation therapy. ClinicalTrials.gov ID: NCT03057288