Visual loss is a rare, but catastrophic, complication of surgery in the prone position. The prone position increases intraocular pressure (IOP), which may lead to visual loss by decreasing perfusion of the anterior optic nerve. We tested whether the reverse Trendelenburg position ameliorates the increase in IOP caused by prone positioning. Furthermore, we compared two prone positioning set ups. The IOP of 10 healthy awake volunteers was measured in the prone position at 3 different degrees of inclination (horizontal, 10 degrees reverse Trendelenburg, and 10 degrees Trendelenburg) and in the sitting and supine positions in a randomized crossover study comparing the Jackson table and the Wilson frame. In a given eye, all prone IOP values (median [25th-75th percentile] exceeded those of the sitting (15.0 mm Hg [12.8-16.3 mm Hg]) and supine (16.8mm Hg [14.0-18.3 mm Hg]) positions. IOPs in the reverse Trendelenburg, horizontal, and Trendelenburg positions were 20.3 mm Hg (16.3-22.5 mm Hg), 22.5 mm Hg (19.8-25.3 mm Hg), and 23.8 mm Hg (21.5-26.3 mm Hg), respectively (P < 0.001 versus reverse Trendelenburg; dagger P < 0.001 versus horizontal). The reverse Trendelenburg position ameliorated the increase in IOP caused by the prone position. Furthermore, the reverse Trendelenburg position decreased the number of grossly abnormal IOP values (>23 mm Hg) by 50% and 75% compared with the prone horizontal and Trendelenburg positions, respectively. The prone positioning setups did not differ in their effect on IOP. The increase in IOP caused by prone positioning was ameliorated by the reverse Trendelenburg position and was aggravated by the Trendelenburg position. The short time period between changes in position and changes in IOP suggests an important role for ocular venous pressures in determining IOP. Therefore, IOP can be beneficially manipulated by operating table inclination in the prone position.