Introduction: Celiac artery compression syndrome (CACS) can be treated successfully by division of the median arcuate ligament and celiac plexus fibers. The standard technique is the open approach by an upper midline or left subcostal incision. Only six single cases in which a laparoscopic transabdominal approach for CACS was used have been reported. We prospectively evaluated the feasibility of the endoscopic retroperitoneal approach for treatment of CACS. Methods: All patients with symptoms suggestive of CACS were evaluated using splanchnic duplex ultrasound scanning, gastric exercise tonometry (GET), and multiplane selective splanchnic angiography. The criteria for treatment were chronic abdominal symptoms, respiratory-dependent CA stenosis, and abnormal GET result. The release was performed by a retroperitoneal endoscopic approach. Anatomic success of the procedure was confirmed by angiography. Results: The endoscopic retroperitoneal approach was used to treat 46 patients with CACS. One patient (2%) required conversion to an open procedure due to suprarenal artery bleeding. Release was ended prematurely in one patient due to a pneumothorax resulting in loss of working space. A postoperative pneumothorax developed in two patients, of which one needed treatment. No other complications were observed. Postoperative angiography during inspiration and expiration showed normal vessel anatomy in 36 of 46 patients. Six of 10 patients with persisting intraluminal stenoses were treated endovascularly. Five of these were successful, which brings the primary-assisted anatomic patency for the total group to 89% (41 of 46 patients). Three patients are being observed, and endovascular treatment remains an option in case of insufficient improvement. On median follow-up of 20 months (range, 2-42 months) 41 patients were free of symptoms or showed significant improvement. Conclusions: The endoscopic retroperitoneal approach for the release of the CA in CACS, with additional endovascular treatment of persistent stenosis, is feasible and effective. Short-term results were comparable with the open procedure.