Surgery of the adrenal glands has various approaches and remains technically challenging. Many different techniques have been used to decrease morbidity. The most important one is probably laparoscopy which has already quite dramatically improved clinical outcome. The second one is the introduction of posterior endoscopic approach (retroperitoneoscopy), which entirely preserves peritoneal integrity. This concept seems to us to be a fundamental in surgery of the retroperitoneum. Recently, new developments have emerged in the field of abdominal surgery. The most radical concept, known as Natural Orifice Transluminal Endoscopic Surgery (NOTES), consists of the introduction of both endoscope and working instruments through natural orifices in order to eliminate skin incisions and their associated morbidities. Although transperitoneal adrenalectomy has previously been reported in a porcine model, here we report our initial experiences of extra-peritoneal transvaginal NOTES approach of the retroperitoneum, focused on the field of adrenal surgery in both porcine and cadaver models. Whether clinical applications will ultimately be derived of this concept is still not clear certainly it raises new possibilities for interesting developments.