INTRODUCTION: Gastric insufflation may be seen in up to 30% of patients receiving non-invasive positive-pressure ventilation (PPV). However, it rarely causes significant observable effects given the integrity of the lower esophageal sphincter, which prevents large amounts of air from entering the gastric lumen. Here we report a rare complication of PPV. CASE DESCRIPTION/METHODS: A 68-year-old male with chronic obstructive pulmonary disorder and chronic kidney disease presented with one week of severe dyspnea, wheezing, and productive cough. The patient received intravenous ceftriaxone, azithromycin, and nebulized albuterol in the ED. Within hours, the patient oxygen saturation decreased to 60% and he became unarousable. The patient underwent tracheal intubation and was extubated the following day. The patient required BIPAP support for the next 4 days. On day 6 of hospitalization, the patient developed severe nausea and diffuse abdominal pain. Clinical examination was significant for firm abdominal distension, diffuse abdominal tenderness without rebound or guarding, and hyperresonance on percussion. Abdominal X-ray revealed a markedly dilated large bowel, concerning for large bowel obstruction versus ileus that was not present on admission (image 1). Subsequent CT imaging of the abdomen and pelvis revealed no free air, but diffuse distension of the proximal, transverse, and sigmoid colon, with the largest segment measuring 10.5 cm, consistent with large bowel ileus (image 2). After receiving multiple enemas and 2 liters of polyethylene glycol/electrolyte solution, the patient passed a significant amount of stool with complete resolution of his abdominal pain and distension. DISCUSSION: Gastrointestinal complications of PPV include stress ulcers, impaired gastric emptying, diarrhea, constipation, obstruction, and rarely, colonic perforation. Those with acute respiratory failure with superimposed COPD are at greater risk for developing ileus due to an increased risk of exaggerated aerophagia. PPV is associated with elevated catecholamines and increased sympathetic activity, which results in splanchnic hypoperfusion. This causes an oxygen supply and demand imbalance in the GI tract, resulting in mucosal damage and alterations in GI motility. In this case, acute colonic pseudo-obstruction developed after 6 days of PPV. It highlights the importance of careful assessment in patients at risk for exaggerated aerophagia due to the risk of colonic ileus and possible perforation.Figure 1.: Left: Chest X-ray on admission showing hyperinflated lungs without colonic dilation. Right: Abdominal X-ray hospital day 6 with colonic dilation.Figure 2.: CT abdomen and pelvis showing diffuse colonic dilation without perforation.