BACKGROUND: With the increasing demand for general anesthesia for endoscopic esophageal procedures, anesthesiologists should understand the clinical characteristics of post-procedural complications (PPCs). METHODS: We retrospectively investigated the incidence of and risk factors associated with PPCs of endoscopic esophageal procedures performed under general anesthesia from July 2013 to November 2016. The final analysis included 129 patients; 114 who underwent esophageal endoscopic dissection for esophageal tumors and 15 cases of peroral endoscopic myotomy for achalasia. Frank perforation during the procedure was defined as an endoscopically recognizable or clinically detected perforation during the procedures. A multivariable logistic regression analysis was conducted to identify independent risk factors for PPCs. RESULTS: The overall incidence of PPCs was 19.4% (25/129). All of the PPCs were managed successfully with conservative measures. The most common PPC was symptomatic, radiologically documented atelectasis (11/25, 44.0%), followed by esophageal perforation-related PPCs (symptomatic pneumomediastinum or pneumoperitoneum; 9/25, 36.0%). In the multivariable analysis, frank perforation during the procedure was the only independent risk factor for PPCs (odds ratio, 8.470, 95% CI, 2.051–34.974, P = 0.003). Although frank perforation during the procedure occurred in 13 patients, 38.5% (5/13) of them did not develop any clinical sequelae after their procedures. Compared with patients without PPCs, patients who developed PPCs took longer to their first oral intake and had prolonged hospital stays (P = 0.047 and 0.026, respectively). CONCLUSIONS: Iatrogenic perforation during endoscopic esophageal procedures under general anesthesia was the only independent risk factor for PPCs; therefore, proactive measures and close follow-up are necessary.