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Purpose: To evaluate the intraocular pressure (IOP) behavior after applying a standardized protocol to induce psychological stress in patients with primary open-angle glaucoma (POAG)., Design: Randomized controlled trial., Participants: A total of 39 patients with POAG were included: 18 in the stress group and 21 in the control group., Methods: Patients were randomized to undergo the Trier Social Stress Test (TSST) or to be included in the control group. All participants were submitted to a modified diurnal tension curve (DTC) 1-4 weeks before randomization, with 3 IOP measurements performed between 8:00 am and 2:00 pm. We evaluated the response to the TSST by measuring the levels of salivary cortisol, salivary amylase, IOP, mean arterial pressure, and heart rate before, immediately after, and 40 minutes after the TSST. The State Trait Anxiety Inventory (STAI) was applied to evaluate the levels of anxiety at the same time intervals., Main Outcome Measures: Changes in IOP (mmHg), salivary cortisol and amylase, heart rate, mean arterial pressure, and STAI scores., Results: At baseline, there were no significant differences between the groups regarding age (P = 0.661), sex (P = 0.669), salivary cortisol (P = 0.104), and mean DTC IOP for the right (P = 0.439) and left (P = 0.576) eyes. We observed a significant mean IOP increase of 3.8 mmHg (right eye; P < 0.001) and 4.1 mmHg (left eye; P < 0.001) when we compared IOP measurements obtained during the DTC and immediately after TSST. Salivary cortisol (5.9 nmol/L; P = 0.004), salivary amylase (323 388 UL; P = 0.004), mean arterial pressure (10.1 mmHg; P < 0.001), and heart rate (12.9 bpm; P < 0.001) also increased significantly after the TSST. In addition, 61.1% (11 of 18) of the patients in the TSST group showed an IOP increase > 4 mmHg following the test. The STAI-state score significantly increased after the TSST compared to baseline (P < 0.001) and decreased from poststress to the recovery period (P < 0.001)., Conclusions: Patients with POAG present significant elevations of IOP, salivary cortisol and amylase, mean arterial pressure, heart rate, and STAI scores after psychological stress induced by the TSST., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)