ObjectiveTo evaluate the effect of peroral endoscopic myotomy (POEM) on perioperative and follow-up outcomes of achalasia patients undergoing unsuccessful prior treatment. MethodsA retrospective analysis was performed on 849 patients with achalasia who underwent POEM and completed follow-up at endoscopy center, Zhongshan Hospital, Fudan University, from August 2010 to December 2014. The effect of POEM was compared between patients with prior treatment (n=245) and those without (n=604). Risk factors for perioperative major adverse events, postoperative clinical reflux and failure were analyzed. ResultsA total of 34 patients (4.0%, 34/849) experienced major adverse events, such as pneumothorax, hydrothorax, delayed bleeding. No statistical difference in major adverse events was found between the two groups [4.5% (11/245) VS 3.8% (23/604), χ2=0.21, P=0.65]. Multivariate logistic regression analysis demonstrated that procedure duration ≥60 min was the independent risk factor for perioperative major adverse events (OR=3.82, 95%CI: 1.81-8.08, P＜0.05), while endoscopist experience >100 cases was the independent protective factor for major adverse events (OR=0.23, 95%CI: 0.07-0.76, P<0.05). During a median follow-up of 23 months (ranging 1-71 months), clinical reflux occurred in 203 patients (23.9%, 203/849), and clinical failure occurred in 94 patients (11.1%, 94/849). Patients with prior treatment had a clinical reflux rate of 26.9% (66/245), which was comparable with those without (22.7%, 137/604) (P=0.19). Multivariate logistic regression analysis demonstrated that Heller myotomy was the independent risk factor for clinical reflux (OR=1.49, 95%CI: 0.98-2.29, P=0.07). Clinical failure rate in patients with prior treatment at 5 years after POEM was 18.0% (44/245), and that in those without was 8.3% (50/604) (P<0.05). Multivariate cox analysis revealed that disease duration ≥10 years (HR=1.62, 95%CI: 1.04-2.52, P=0.03) and prior treatment (HR=1.90, 95%CI: 1.26-2.88, P<0.05) were independent risk factors for clinical failure. Conclusion POEM is an effective and safe rescue for patients who underwent unsuccessful prior treatment, with a low rate of perioperative major adverse events and good long-term effects. Prior treatment may increase the risk for clinical failure of POEM, it may not significantly increase severe perioperative complications or clinical reflux though.