To use multiple data sources to determine drivers of patient adherence to topical ocular hypotensive therapy. Retrospective database and chart reviews in combination with prospective patient surveys. Diverse medical environments where insured patients in the research database seek care. Three hundred patients with a new claim diagnosis for open-angle glaucoma who initially were prescribed one of three prostaglandins and 103 physicians participating in the same medical plans. A structured interview addressing self-reported adherence, experiences with medication, communication with the physician, and health-related beliefs associated with adherence behavior was administered to surveyed patients. Phone interviews were conducted with participating ophthalmologists. Of adherence, medication possession ratio. Eight variables were associated independently with a lower medication possession ratio: (1) hearing all of what you know about glaucoma from your doctor (compared with some or nothing); (2) not believing that reduced vision is a risk of not taking medication as recommended; (3) having a problem paying for medications; (4) difficulty while traveling or away from home; (5) not acknowledging stinging and burning; (6) being nonwhite; (7) receiving samples; and (8) not receiving a phone call visit reminder. The multivariate model explained 21% of the variance. These findings indicate that doctor-patient communications and health-related beliefs of patients contribute to patient adherence. Patient learning styles that are associated with less concern about the future effects of glaucoma and the risks of not taking medications are associated with lower adherence. Specifically, knowledge about potential vision loss from glaucoma is a critical element that tends to be missed by more passive doctor-dependent patients who tend to be poorly adherent. These findings suggest that educational efforts in the office may improve patient adherence to medical therapies.