While endoscopic ultrasound (EUS)-guided fiducial placement is technically feasible, its role in the delivery of image-guided radiation therapy (IGRT) is unclear. In this study, we evaluated the feasibility and safety of using EUS-guided fiducial markers for delivering IGRT in patients with pancreatic cancer. Following computed tomography (CT) simulation, a radiation therapy treatment plan was prepared for each patient. A kilovoltage (kv) image obtained before each treatment session was aligned with images generated during treatment planning, based on the position of fiducials. Radiation therapy was then delivered. Image analysis was also performed by alignment of bony landmarks (current standard of care). Daily shifts of fiducials between the two sets of images represented movement of the pancreas relative to the bony landmarks. EUS-guided fiducial placement was technically successful in all nine patients and no complications were encountered. The fiducials were easily identified for image fusion and IGRT was delivered successfully to all patients. The movement of the pancreas relative to bones was 0.2cm (0.10.5cm), 0.5cm (0.21.5cm), and 0.4cm (0.20.9cm) in the anteriorposterior, superiorinferior, and leftright axes, respectively. This technique may have significant clinical implications in terms of radiation dosimetry. © Georg Thieme Verlag KG Stuttgart - New York.