Reducing access size and trauma are important issues in natural orifice transluminal endoscopic surgery (NOTES). The combination of experience with laparoscopic colorectal surgery and transanal endoscopic microsurgery has helped in the use of the transanal approach as a realistic option of NOTES techniques to introduce transanal hybrid laparoscopic-assisted colon resection into clinical practice. The purpose of this study was to assess the clinical introduction of transanal hybrid colon resection in terms of feasibility and patient safety. Patients with pelvic floor disorders, prolapse, and slow-transit constipation in whom a colon resection was indicated were recruited. Patients were followed prospectively with a postoperative well-being score, a pain score, and a quality-of-life score. All complications were prospectively documented. The essential change was the reduction of the number and size of ports by using the transanal route. A camera and two 5-mm ports for grasping forceps and delivering ultrasonic energy were the laparoscopic components. All tasks requiring a port diameter of >5 mm were applied via the transanal route, such as positioning of the proximal stapler anvil, application of linear stapling for resection, specimen retrieval, stapler anastomosis, and closing the bowel. Fifteen patients with benign colorectal disease underwent transanal hybrid colon resection, and 11 had additional rectopexy. All patients were women with a mean age of 61 (range, 28-86) years and a body mass index of 26 kg/m(2). One patient was converted to full laparoscopy. One complication--bleeding that required no reintervention--was recorded. The procedure lasted a mean of 131 (range, 55-184) min. The Gastrointestinal Quality of Life Index was 96 before surgery and 117 after surgery. From this initial experience, transanal hybrid colon resection seems a feasible and safe hybrid NOTES procedure that can be usefully introduced into clinical practice.