PURPOSE: Natural orifice transluminal endoscopic surgery (NOTES) is a new operation technique that utilizes natural orifices of the patient's body with the intention to puncture hollow viscera in order to insert an endoscope into a peritoneal cavity for incisionless surgery. The aim of this study was to evaluate the safety and feasibility of endoscopic cecectomy through the rectum in one dog and the vagina in another dog. METHODS: This study was performed in two beagle dogs for rectal and vaginal approaches. A five-milimeter trocar was inserted into the abdominal cavity by the Hasson method and intra-abdominal pressure was maintained at 5 mmHg with CO2. After pneumoperitoneum was accomplished, the rectum or vagina was incised with a needle knife and a one-channel gastric endoscope was inserted into the abdominal cavity. Counter-traction was performed using a laparoscopic grasper introduced via the 5 mm trocar in the umbilicus. The cecum was dissected from the base by using a needle knife with the aid of laparoscopic counter-traction. The resected cecum was retrieved through the anus or vagina without pouch bag. The incised rectum was closed by using 90-degree endoclips whereas the incised vagina was not repaired. RESULTS: Cecectomies were successfully performed with both transrectal and transvaginal routes. Both cases had no complication and recovered from surgery uneventfully. CONCLUSION: Endoscopic cecectomy with hybrid NOTES are feasible and safe. With the improvement of surgical experiences and further instrumental development, NOTES can be one option for human intestinal surgery.