After removal of four impacted third molars under general anesthesia, our patient developed subcutaneous emphysema, pneumothorax, pneumopericardium, and pneumomediastinum. Soon thereafter, coma with generalized epileptic status ensued. A cerebral magnetic resonance and single photon emission computed tomography showed hypoperfusion of the right thalamus and parietal, temporal, and frontal cortices. The likely mechanism was injection of air by the high-speed dental drill through the soft tissue adjacent to the roots of the lower molars. We were unable to find any previous report of systemic air embolism after oral surgery.