Background and aimsGastric per-oral endoscopic myotomy (G-POEM) is a new therapeutic option for the treatment of refractory gastroparesis. However, the outcome of G-POEM after the failure of gastric electrical stimulation (GES) or other pylorus-targeting therapies has been poorly reported. MethodsData were collected from patients referred for G-POEM for refractory gastroparesis. The efficacy in patients with previous interventional techniques was compared to patients naïve to instrumental technique. The primary endpoint was the 6-month clinical success rate, defined as at least a 1-point decrease in the Gastroparesis Cardinal Symptom Index (GCSI). ResultsAmong 48 patients referred for G-POEM, 32 patients had had previous instrumental treatments (66%): 15 (31%) had had GES, and 17 (35%) had had pyloric endoscopic dilation or toxin injection. The technical success rate was 100%. At 6 months, clinical success was achieved in 25/48 patients (52%) and the GCSI decreased from 3.38 (2.94–3.95) to 2.25 (1.11–3.36) (p < 0.001). The 6-month success rate was similar in patients with or without previous instrumental treatment (50.0% vs 56.3%; p = 0.41). The complication rate was also similar in the two groups (6.3% vs 12.5%; p = 0.59), with only one severe adverse event. The only predictive factor for success at 6 months was a higher body mass index (OR = 1.14 [1.01–1.32]; p = 0.05). ConclusionG-POEM is safe and remains effective after GES or previous pyloric treatment failure, with 50% efficacy at 6 months. The therapeutic strategy in refractory gastroparesis remains to be defined.