Purpose The Trendelenburg position has a dramatic effect on circulation, consequently increasing cerebral and intraocular pressure. We evaluated whether modifying the Trendelenburg position would minimize the increase in intraocular pressure. Materials and Methods In this prospective, randomized, controlled study we compared intraocular pressure in patients undergoing robot-assisted laparoscopic radical prostatectomy while in the Trendelenburg position or the modified Z Trendelenburg position. In group 1 intraocular pressure, blood pressure and endotracheal CO2 were measured in the patient at anesthesia induction (time 1), before positioning (time 2), and while in the Trendelenburg position (time 3) and in the modified Z Trendelenburg position (time 4). They were also measured after pneumoperitoneum (time 5), every 30 minutes (times 6 to 16), while supine at the end of pneumoperitoneum (time 17) and before awakening (time 18). We modified the Trendelenburg position by placing the head and shoulders horizontally. Results Group 1 included 29 patients in the modified Z Trendelenburg position. Group 2 included 21 patients in the Trendelenburg position. No difference was found in patient demographics or surgical outcomes. Median intraocular pressure was in the low normal range at times 1 and 2, and increased in time 3 in each group. From time 4 intraocular pressure decreased and at all time points it was significantly lower in group 1 by a mean of 4.61 mm Hg (95% CI -6.90-2.30, p <0.001). At time 17 mean intraocular pressure decreased to normal (19.6 mm Hg) in group 1 but remained in the hypertensive range (24.9 mm Hg) in group 2. At time 18 mean intraocular pressure was 17 mm Hg in each group. Blood pressure was significantly lower in group 1 with a mean reduction in systolic and diastolic pressure of 6.3 and 4.3 mm Hg, respectively. Conclusions Our results suggest that modifying the Trendelenburg position during robot-assisted laparoscopic radical prostatectomy has a significant positive effect on patient neuro-ocular safety by lowering intraocular pressure and accelerating its recovery to the normal range without affecting the operation.