The real-world pharmacological use of netarsudil shows that it can produce a clinically significant decrease in intraocular pressure for a small group of patients, even if they are already taking three or four other hypotensive glaucoma medication classes. This study aimed to assess the effectiveness of netarsudil in reducing intraocular pressure among veterans with advanced glaucoma on maximally tolerated medical therapy. All patients with glaucoma who received netarsudil between June 2018 and April 2020 from the West Los Angeles Veterans Administration Medical Center were reviewed. Inclusion criteria included a minimum of one intraocular pressure measurement in each of two time windows (within and after 4 months of netarsudil use). Exclusion criteria included medication nonadherence, change in treatment plan before post-treatment intraocular pressure could be obtained, corneal disease precluding reliable measurement, outside follow-up, and loss to follow-up. Intraocular pressure at baseline and that at two time windows were compared using analyses of variance. Relationships between intraocular pressure and number of baseline medications and concurrent statin therapy were evaluated. Netarsudil tolerability was reported. Of 200 patients prescribed netarsudil, 42 patients (eyes) met the enrollment criteria. The mean age of these patients was 75.7 years (95% confidence interval [CI], 73.0 to 78.4 years), 64% were of African descent, 79% had open-angle glaucoma, and the mean number of baseline medications was 3.7 (95% CI, 3.5 to 3.9). Baseline intraocular pressure of 17.2 mmHg (95% CI, 16.1 to 18.2 mmHg) decreased to 15.1 mmHg (95% CI, 14.0 to 16.2 mmHg; P < .001), and a reduction of >20% was seen in 30.9% of patient after 4 months of netarsudil therapy. Intraocular pressure reduction was not associated with number of baseline medications or systemic statin use. Netarsudil may produce a clinically significant intraocular pressure reduction in up to a third of the patients with advanced glaucoma already on maximally tolerated medical therapy.