A 69-year-old woman underwent hyperbaric oxygen therapy because of a nonhealing ulcer of her foot. During decompression, she developed a left-sided hemiplegia and confusion. Recompression resulted in transient neurologic improvement, but she eventually became comatose. Ventricular dysrhythmias developed and she died without regaining consciousness 17 h after onset of symptoms. An autopsy revealed diffuse interstitial pulmonary fibrosis with severe paracicatricial emphysema, chronic interstitial inflammation, and chronic bronchitis with abundant intrabronchial mucus. There was extensive multifocal ischemic injury of the cerebral cortex. The hippocampi, basal ganglia, and cerebellum were spared. Scattered acute myofiber necrosis was present in the heart. Clinical presentation and autopsy findings strongly support the diagnosis of air embolism and illustrate a potential risk of hyperbaric oxygen therapy in patients with preexisting pulmonary disease.