BACKGROUND OR PURPOSE: Peroral endoscopic myotomy (POEM) has revolutionized the therapeutic landscape for esophageal achalasia, offering efficacy comparable to surgery with the convenience of an endoscopic approach. With the growing popularity of POEM, insufflation-related adverse events present unique challenges that have been widely discussed in the literature. This study aimed to investigate the safety profiles and risk factors linked to insufflation-related events in patients undergoing POEM in endoscopy suites. METHODS: This retrospective analysis included 100 consecutive patients with achalasia treated by POEM at our institute between March 2016 and October 2022. All procedures were conducted in an endoscopy suite and employed CO RESULTS: All procedures were successfully performed with an average POEM duration of 92.3minutes and an average anesthesia duration of 108.4minutes. One major adverse event involving an esophageal leak and requiring endoscopic stenting was observed, along with a 27% incidence of minor adverse events. Insufflation-related events, manifesting as capnoperitoneum, subcutaneous emphysema, or capnomediastinum, were identified in 48% of cases, but none required additional interventions or extended hospitalization. A peak airway pressure increase of 20% or more was identified as the only predictor for insufflation-related events. CONCLUSIONS: Performing POEM in an endoscopy suite can generally be considered safe from major adverse events related to insufflation. Monitoring peak airway pressure for a 20% increase may be an early indicator for other potential insufflation-related events.