Background Cerebral arterial air embolism is a life-threatening complication that can result in neurologic deficits or death. Sometimes it is iatrogenic, presented as a complication of invasive medical procedures. Here we describe a case of cerebral arterial air embolism secondary to iatrogenic left atrial-esophageal fistula, of which the diagnosis might be covered up by the complicated pathophysiologic changes. Case presentation A 68-year-old man presented with unconsciousness hours after aphasia and right hemiplegia, accompanied with hematemesis and fever. He had a history of atrial fibrillation, treated by radiofrequency catheter ablation 1 month ago. Brain CT displayed massive air embolism in left hemisphere, as well as right parietal lobe. Chest CT demonstrated a focus of air in the left atrium, which highly suggested an atrial-esophageal fistula. The patient received high flow (6 L/min) oxygen therapy. Intravenous antibiotics including imipenem and vancomycin were administered together with crystalloid rehydration. Supportive therapies were given including intubation, mechanical ventilation and vasopressor use. Because of the patient's unstable condition and poor prognosis, surgical repair was considered but not pursued. The patient presented a very fast deterioration of cardiac function and circulatory failure, and finally died from cardiac arrest. Conclusions Clinicians must have a high index of suspicion for atrial-esophageal fistula for patients presenting with chest discomfort, new onset of stroke, upper gastrointestinal bleeding, and development of sepsis as long as 50 days after the ablation for atrial fibrillation. Urgent CT can ultimately establish the diagnosis in most cases.