OBJECTIVE To report a rare case of periorbital emphysema concurrent with cervicofacial and mediastinal emphysema in an elderly woman who underwent upper gastrointestinal endoscopy for chronic liver disease. METHODS An elderly woman with decompensated chronic liver disease presented with features of periorbital, facial, and mediastinal emphysema, characterized with crepitant swelling over the right periorbital area, face, neck, and mediastinum after undergoing upper gastrointestinal endoscopy. There was no history of trauma or Valsalva maneuver. Ocular findings were stable with no evidence of orbital compartmental syndrome. Urgent computed tomography scans of the orbit and chest were performed, and emergency systemic treatment with nasogastric decompression and antibiotics was initiated. However, she suddenly collapsed and succumbed despite all resuscitative efforts. CONCLUSIONS Our case demonstrates that periorbital emphysema can occur following procedures such as upper gastrointestinal endoscopy, in the eyes without history of local trauma. This complication should be suspected especially if there is associated cervicofacial and mediastinal emphysema. Subcutaneous emphysema is usually self-resolving; however, extension of air into deeper planes can cause dangerous complications such as blindness due to orbital emphysema or mortality due to mediastinal emphysema. Hence, prompt diagnosis and urgent intervention are crucial to avoid vision and life threatening complications.