Background: Stereotactic radiation by using fiducial markers permits higher doses of radiation while reducing the exposure of uninvolved, adjacent structures. EUS has been used to deploy fiducials, although a 19-gauge needle has traditionally been required. Objective: To report a new technique and the feasibility of deploying a fiducial compatible with a 22-gauge needle under EUS guidance. Design: Single-center, case series. Setting: Tertiary care referral center. Patients: Thirteen patients with primary or metastatic cancer referred for stereotactic radiation. Interventions: EUS-guided placement of a single fiducial marker that is compatible with a 22-gauge EUS-FNA needle. Main Outcome Measurements: Technical success and complications. Results: Thirteen patients referred for EUS-guided placement of a fiducial marker were identified in the endoscopic database. Targeted lesions measured 27 ± 13 mm (range 8-50) × 21 ± 10 mm (range 6-42). All fiducials were successfully deployed, 9 using a transgastric and 4 using a transduodenal approach. There were no EUS-associated complications. Two patients did not proceed to radiation therapy as a result of interval peritoneal metastasis. However, all fiducials were visible on the roentogram. Eleven of 13 patients (85%) required placement of 1 fiducial, whereas 2 patients (15%) required 2 fiducials. Limitations: Uncontrolled feasibility study with limited sample size and follow-up. Conclusion: EUS-guided placement of a fiducial using a 22-gauge needle is technically feasible and may permit greater access compared with the 19-gauge needle technique.