OBJECTIVES: To find out the persistence degree (period of time of continuous therapy with the drug prescribed) of glaucoma patients treated with prostaglandin (latanoprost, bimatoprost, and travoprost), or ß-blocker (timolol) monotherapy. METHODS: An observational and retrospective study was conducted of a 24-month follow-up in 191 patients (from 4 centers), to examine the time elapsed until patients’ withdrawal from therapy. The required parameters were obtained from patients’ medical records. A descriptive analysis, a Kaplan-Meier survival analysis, and a Cox regression model were used to determine which was the drug related to a greater persistence degree, and to detect variables significantly influencing persistence in these patients. RESULTS: In both the descriptive analysis and the survival curves, latanoprost was associated with a higher persistence degree in the glaucoma treatment: 81.6% vs. 22.9% for bimatoprost, 65.4% for travoprost and 60.5% for timolol (p<0.0001). The persistence degree was significantly influenced by the following variables: the antiglaucoma agent used as monotherapy, with a six-fold higher risk of treatment withdrawal during the follow-up period due to receiving travoprost instead of latanoprost (p<0.0001); and the age (p=0.001). Even though comorbidities did not indicated to be directly related to persistence, their occurrence was related to age. The main reasons for treatment withdrawal were lack of efficacy and the existence of intolerance and/or adverse events, significantly superiors in the bimatoprost group, 28.6% (p<0.001) and 48.6% (p<0.001), respectively. CONCLUSIONS: Latanoprost shows a higher persistence degree compared to travoprost, bimatoprost and timolol in routine clinical practice, resulting in a better control of IOP and lower associated costs, improving the health care quality of glaucomatous patients and considerable resources saving for the National Health System.