Objective: To explore whether oral statin and other antihyperlipidemic medications are associated with open-angle glaucoma. Methods: The administrative clinical databases maintained at the Veterans Affairs Medical Center, Birmingham, Ala, were used to conduct a matched case-control study. Cases were all male patients aged 50 years and older with a new diagnosis of glaucoma on an outpatient or inpatient visit during the periodJanuary 1, 1997, through December 31, 2001. Ten control subjects were matched to each case according to age (within 1 year). Prescription files were assessed for statin use as well as additional medications to lower cholesterol levels. Information on comorbid medical conditions was also obtained. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Longer duration of statin use was associated with a lower risk of open-angle glaucoma (P for trend = .04) primarily among subjects with 24 months or more of use (OR, 0.60; 95% CI, 0.39-0.92). When stratified by comorbid medical condition, among those with cardiovascular disease (OR, 0.63; 95% CI, 0.42-0.97), lipid metabolism disorders (OR, 0.63; 95% CI, 0.41-0.99), and the absence of cerebrovascular disease (OR, 0.76; 95% CI, 0.58-0.99), statins demonstrated a protective effect on open-angle glaucoma. Finally, a protective association was also observed among those who used nonstatin cholesterol-lowering agents (OR, 0.59; 95% CI, 0.37-0.97). Conclusions: Initial examination of an administrative clinical database indicates the intriguing possibility that long-term use of oral statins may be associated with a reduced risk of open-angle glaucoma, particularly among those with cardiovascular and lipid diseases. Nonstatin cholesterol-lowering agents were also associated with a reduced risk of having open-angle glaucoma. Additional investigation is warranted as to whether these classes of agents may provide an additional therapeutic addition for glaucoma.