Background and Aim Laparoscopic hysterectomy (LH) have been frequently used because of low complication rates and short duration of hospital stay. Elevated intracranial pressure (ICP), a disadvantage of laparoscopic surgery, is caused by the Trendelenburg position (TP) and CO2 pneumoperitoneum (PP). This study aimed to evaluate TP and PP associated changes in ICP by ONSD measurements during LH. The intra-and inter-observer consistency and reliability of ONSD measurements were also investigated. Methods Sixty patients with were enrolled into this prospective study. ONSD for each patient was measured by three anesthesiologists at T0, T1, T2, and T3 time points. ONSD, mean arterial pressure (MAP), end tidal CO2 (EtCO2), and arterial blood CO2 partial pressure values (PaCO2) were measured at T0: baseline, T1: 10 min after introducing 20 mmHg PP, T2: 10 min after placing the patient in TP and 15 mmHg PP and, T3: 10 min after PP deflation. Results The ONSD measured at T1 (5.97 +/- 0.49 cm) and T2 (5.95 +/- 0.57 cm) were higher than T0 (5.63 +/- 0.53 cm) and T3 (5.72 +/- 0.47 cm) (p < 0.05). There were no correlations between MAP and ONSD, and also between PaCO2, EtCO2, and ONSD measurements at any time points. Inter-observer intraclass correlation coefficient (ICC) values of ONSD measurements by all examiners had moderate (at T1) to good (at T0, T2, T3) reliability. Intra-observer agreements were reasonable for each observer. Conclusion ONSD measurements increase with CO2PP and TP in patients undergoing LH. Transorbital sonography is a reliable method to monitor intraoperative changes in ONSDs. This study underlines the need for careful training and the importance of standardization in order to obtain reliable results in the examination technique of ONSD measurements.