Objective To evaluate the feasibility, safety, and efficacy of repeat peroral endoscopic myotomy (Re-POEM) as salvage therapy after initial POEM failure. Methods Thirty-three patients with persistence/recurrence of symptoms after previous POEM (Eckardt symptom score≥4) were retrospectively selected from a maintained database housing a total of 2516 consecutive patients with achalasia. The primary endpoint was symptom relief during follow-up, defined by an Eckardt score of ≤3. Secondary outcome measures were procedure-related adverse events, change in manometric lower esophageal sphincter (LES) pressure, and reflux symptoms before and after Re-POEM. Results All patients underwent successful Re-POEM a mean of 18.6 months (range3–55 months) after execution of their primary POEM procedures. Mean operative time was 45.1 minutes (range 28–64 minutes). One instance of submucosal tunnel infection was successfully managed with conservative treatment. During a mean follow-up period of 36.6months (range 12–58 months), symptom relief was achieved in all patients. The mean symptom score pretreatment was 5.5 (range 4–8), compared with a post-treatment mean of 1.3 (range 0–3;P< 0.001). Mean LES pressure also declined from 26.0 mmHg to 9.6mmHg after Re-POEM (P< 0.001). The overall clinical reflux complication rate of Re-POEM was 33.3%(11/33) Conclusions Re-POEM appears safe and effective as a salvage option after initial POEM failure, conferring short-term symptom relief and being free of serious complications in all patients.