BACKGROUND: Peroral endoscopic myotomy has been developed to provide a less invasive treatment for oesophageal achalasia compared to surgical cardiomyotomy. AIMS: To report our initial experience on feasibility, safety and clinical efficacy of peroral endoscopic myotomy. METHODS: Eleven patients (eight women, mean age 32, range 24-58) underwent an attempt at peroral endoscopic myotomy under general anaesthesia. After submucosal injection, a mucosal entry into the oesophageal submucosa, and a tunnel extending to the oesophagogastric junction and beyond into the stomach were created (total mean length: 15±1.7cm). Myotomy of the circular oesophageal and gastric muscle bundles was then achieved under direct vision (total mean length: 10.2±2.8cm). Haemostatic clips were used to close the mucosal entry. The Eckardt Score and manometry were used to evaluate the results. RESULTS: Peroral endoscopic myotomy could be completed in 10 out of 11 patients (91%). Mean procedure time was 100.7min (range 75-140min). No major complication occurred. Clinical success was achieved in all patients at 1-month follow-up (Eckardt Score 7.1 vs. 1.1, p=0). Lower oesophageal sphincter pressure decreased from 45.1 to 16.9mmHg (p=0). CONCLUSIONS: This initial experience with peroral endoscopic myotomy shows its safety and efficacy in the treatment of achalasia. Further studies are warranted to assess the long-term efficacy and to compare peroral endoscopic myotomy with other treatment modalities.