In a clinical series, 10 consecutive female patients with intra-abdominal infections were successfully treated with natural orifice transluminal endoscopic surgery (NOTES) performed transvaginally. The surgery, which consisted of a hybrid NOTES procedure using a transvaginal approach, was performed on an emergency basis by the surgical team on call. The indications for surgery were acute cholecystitis (n = 6), acute appendicitis (n = 2), and pelvic peritonitis (n = 2) with intra-abdominal infection. The procedure was successfully performed in all patients using a dual-channel endoscope and mini-laparoscopy assistance. This is the first clinical series in which NOTES has been performed on an emergency basis to treat intra-abdominal infections. Transvaginal surgery for intra-abdominal infection is a feasible procedure for groups experienced in the elective NOTES approach.