OBJECTIVES: The measurement of patient compliance to medications in a large database analysis presents inherent challenges, such as concomitant prescriptions, switches and add-ons. The Medication Coverage (MC) methodology is an application of the Medication Possession Ratio (MPR) that allows for consideration of multiple prescriptions simultaneously or serially. The benefits of this approach to outcomes research are explored. METHODS: In 3864 patients with primary open-angle glaucoma (POAG), a prescription for a glaucoma medication, and a minimum 2 years of continuous enrollment post-index date (date of first glaucoma therapy) were identified within the PharMetrics database. MC was calculated as the proportion of days a patient was in possession of any glaucoma medication during the first year of follow-up. Medication possession on each day was considered as a binomial variable (presence or absence of medication), independent of whether patients were on one or multiple medications. We designated the 75th percentile of the MC score to stratify patients as “more” versus “less” compliant. “More Compliant” was then tested as a predictor in multivariate logistic models, while controlling for key covariates, predicting ocular surgery in year two of follow-up. RESULTS: The MC methodology applied in this sample data showed that mean MC was 0.47 and 75th percentile MC was 0.67. Coverage was normally distributed. Logistic regression models showed that as severity of POAG patients increases, compliance with pharmacotherapies is increasingly associated with a reduced risk of glaucoma surgery. CONCLUSIONS: MC can be used to examine patient compliance with medication in large retrospective database analyses. This technique allows for analysis of patient compliance to medication while considering concomitant medications and various treatment patterns.