The researchers sought to find a link between health literacy and successful glaucoma drop administration for research. A single-site interventional randomized controlled trial’s design substudy was conducted. If they endorsed poor drop adherence, veterans getting care at the Durham Veterans Affairs Eye Clinic with an open-angle glaucoma diagnosis were recruited. The Rapid Estimate of Adult Literacy in Medicine (REALM) was used to assess participants’ health literacy, as well as a qualitative assessment of eye drop delivery method using 3 different criteria: (1) Only 1 drop, was dispensed, (2) the bottle was not potentially contaminated, and (3) the drop was put in the eye. After correcting for age, disease severity, and the Veterans Administration Care Assessment Needs (CAN) score, a multivariate logistic regression model was performed to investigate the relationship between REALM score and effective drop administration. Successful drop administration was the primary outcome measure. Furthermore, 78% of the 179 participants with REALM results and observed drop administration read at or above the high school level (HSL), while 22% read below HSL. 87% (n=156) of the 179 individuals effectively instilled the drop into the eye (criterion 1). Compared to those reading at less than HSL, a higher proportion of individuals who read at HSL or higher effectively instilled the drop in the eye (90.6% vs 75.0%; P=0.02). Across varied levels of visual field severity, success rates with criteria 1 were similar. The difference in Care Assessment Needs scores between those who had a successful overall drop method and those who did not was not statistically significant. Poor health literacy was linked to a lower rate of effective drop instillation in glaucoma patients. In a vulnerable group, screening for and considering health literacy while devising interventions to promote glaucoma self-management might have improved medication adherence.