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To review natural orifice translumenal endoscopic surgery (NOTES) applications in clinical practice and assess the evidence base for each application as reported in the literature. An electronic literature search was performed. Inclusion criteria were publications relating to NOTES applications in humans. For each type of operation the highest level of evidence available for clinical NOTES publications was evaluated. Morbidity and short-term operative outcomes were compared with gold standard published evidence where available. Finally, registered trials recruiting patients for NOTES applications were identified. Human NOTES publications with the highest level of evidence in each application are identified. There were no RCTs in the literature to date. The strongest evidence came in the form of large, multi-centre trials with 300-500 patients. The results are encouraging, comparable with gold standard techniques on morbidity and mortality. While short-term operative outcomes were also similar when compared to the gold standard techniques, other than improved cosmesis little else can definitely be concluded as a clear benefit of a NOTES procedure. The most common procedures are cholecystectomy, appendicectomy and peritoneoscopy mainly performed via transvaginal access. It is evident that morbidity appears to be higher when the transgastric route is used. The safety profile of hybrid NOTES transvaginal procedures is beginning to be confirmed as is evident from the large number of procedures presented in this review. A number of authors have presented work on pure NOTES procedures but the results are inconsistent and thus the vast majority of NOTES procedures worldwide are performed in a hybrid fashion with a variable amount of laparoscopy. This review of the clinical applications of NOTES summarises the growing evidence behind this surgical discipline and highlights NOTES procedures with an acceptable safety profile.