Abdominal surgery has traditionally been performed through large incisions into the peritoneal cavity. In the past decade, traditional open surgery has been increasingly replaced by minimally invasive laparoscopic and robotic techniques. In comparison to open surgery, these approaches can decrease postoperative pain, shorten the convalescence period, and improve cosmesis. Nonetheless, these techniques require multiple small entry incisions and are therefore associated with risk of wound infection and incisional hernia. The latest surgical advance is performance of procedures via natural body openings such as the mouth, anus, vagina, and bladder. To date, clinical experience with natural orifice translumenal endoscopic surgery (NOTES) is extremely limited. Herein, we describe the initial clinical case in which we evaluated the bladder as a portal for NOTES. Our experience indicates clinical feasibility of transvesical peritoneoscopy with existing clinical equipment, but additional refinements of the technique and associated instrumentation appear warranted. In comparison to other portals, the urinary tract seems to have distinct clinical advantages for NOTES.