OBJECTIVE: Laparoscopic Heller myotomy (LHM) provides more durable relief of achalasia symptoms than endoscopic pneumatic dilation or botulinum toxin injection. The role of pre-operative endoscopic therapy in surgical candidates is controversial. We investigated the association between multiple pre-operative endoscopic interventions and objective and subjective outcomes after LHM for achalasia.METHODS: Patients undergoing first-time LHM for achalasia between November 2001 and January 2008 were included. Demographics, comorbidities, pre-operative therapy, operative details, and clinical follow-up were obtained by chart review. Gastrointestinal (GI) symptom profile and health-related quality of life (HRQOL) was assessed pre-operatively using the GERD Symptom Assessment Scale (GSAS) and Short Form-36 (SF-36), respectively. Patients were classified on the number of pre-operative endoscopic interventions: zero or one intervention (group 1) versus two or more interventions (group 2). Outcomes were assessed at a median of 22 months post-operatively using mailed GSAS, SF-36, and achalasia-specific questionnaires. The primary outcome of interest was surgical failure, defined as requiring additional surgical or interventional endoscopic therapy. Secondary outcomes of interest included gastroparesis and changes in GI symptoms and HRQOL.RESULTS: 134 patients met inclusion criteria; 88 (66%) were in group 1 and 46 (34%) in group 2. At the time of operation, patients in group 2 had a longer duration of symptoms (median 36 vs. 21 mos., p=0.0026) and higher ASA classification (40% vs. 19% ASA 3-4, p=0.009) than those in group 1. No perioperative leaks or deaths occurred in either group. Group 1 patients reported significant improvements in SF-36 bodily pain, energy, social function, and general health scores, while HRQOL in group 2 remained unchanged. Five patients (3.7%) were diagnosed with symptomatic gastroparesis post-operatively. Surgical failure rate was 14.2%, and was higher in group 2 vs. group 1 (28.3% vs. 6.8%, p=0.001). On logistic regression modeling with adjustment for confounders, having >1 pre-operative endoscopic intervention was found to be a significant independent predictor of surgical failure (OR=5.26, 95% C.I. 1.61-17.17, p=0.006). CONCLUSIONS: Multiple pre-operative endoscopic interventions are independently associated with a higher surgical failure rate after LHM for achalasia, suggesting that repeated interventions should be reserved only for patients who fail surgical therapy or are not surgical candidates. Potential associations between endoscopic intervention, gastroparesis, and LHM need further study.