Air embolism is a rare complication of gastrointestinal endoscopy. We present a 56-year-old male who developed both venous and systemic arterial air embolism during an endoscopic retrograde cholangiopancreatogram. Despite early treatment based on clinical diagnosis and confirmation by transthoracic echocardiography, the patient died as a result of severe cerebral ischaemia. Risk factors associated with air embolism in gastrointestinal endoscopic procedures include situations where the mucosa is not intact or where high pressures are generated in the lumen of the gastrointestinal tract. Clinical diagnosis of air embolism during endoscopy is difficult and urgent echocardiography is the investigation of choice. Treatment is largely supportive but hyperbaric oxygen therapy should be considered in any severe cases, especially if neurological injury is present.