Introduction: Transcranial sonography (TCS) is a bedside examination which is currently used in multiple neurocritical care settings. Third ventricle ultrasound is usually a simple technique, though a large insonation angle could lead to an overestimation of third ventricular diameter. The aim of this study was to use a mathematical model to evaluate the impact of probe inclination on the false positive rate when using TCS to evaluate third ventricle enlargement., Methods: Using R software, we simulated a pool of 100,000 fictitious patients with a normal third ventricle size (diameter from 0 to 9 mm) in daily follow-up for ventricle enlargement for 30 consecutive days using TCS. Each day, a different, random insonation angle (α) was generated and a corresponding measured diameter calculated as: measured diameter=real diameter/cos α. If the measured diameter was >9.0 mm, the simulation registered a "misdiagnosis" episode and the simulation loop was interrupted; otherwise, the simulation continued to its thirtieth iteration., Results: Of the 100,000 "patient" simulations, 30,905 (30.9%) had an erroneous TCS diagnosis of ventricular enlargement. Angles of insonation >35 degrees contributed to 79.3% of the total misdiagnoses of ventricular enlargement (false positive rate, 3.71%), whereas misdiagnosis was rare when the insonation angle was ≤15 degrees (1.30% of the total misdiagnoses; false positive rate, 0.06%)., Conclusion: Using probe inclinations <15 degrees, erroneous diagnosis of third ventricular enlargement was rare. Our results suggest that TCS has a low rate of false positives when the angle of insonation is minimized., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)