We report a case of possible air embolism during a three-port pars plana vitrectomy and air-fluid exchange of the vitreous cavity of the eye. After the start of intraocular air flushing, sudden tachycardia, a decrease in oxygen saturation and end-tidal carbon dioxide tension, and a distinct "mill-wheel" murmur were observed. Venous air embolism was suspected but other sources of air entry into the circulation and a thromboembolic event were excluded. Once intraocular air flushing was ceased, clinical variables returned to normal within minutes. In conclusion, during air-fluid exchange of the vitreous cavity, air embolism should be considered as a possible rare complication.