Complications related by upper endoscopy include bleeding, perforation and infections but they are rare on simply diagnostic endoscopy. Duodenal perforation is less common but mortality rates are high. Diagnosis is based on keeping high suspicion that makes early detection to offer optimal treatments and better outcomes. Surgical intervention is standard treatment but some cases could benefit from conservative care. However, there was little literature description of afferent loop perforation after upper endoscopy. Herein, we report a case of pneumomediastinum, pneumoperitoneum, and pneumoretroperitoneum secondary to afferent loop perforation after upper endoscopy in patient with Billroth II gastrectomy. This rare case should be the reminder for physicians carefully performing upper endoscopy in patients with Billroth-II gastrectomy and keeping high suspicion of perforation after endoscopy if abdominal pain.