The purpose of this study was to compare 2% dorzolamide three times daily with 2% pilocarpine four times daily to determine patient preference, tolerability, and impact on daily life in patients concurrently receiving 0.5% timolol twice daily for treatment of elevated intraocular pressure (IOP). Seventy-five patients were enrolled in this 4-week, randomized, two-period, crossover study. The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to assess patient preference and perception of side effects and activity limitations resulting from the study medications. IOP measurements were obtained 2 hours after drops were instilled and visual field tests were performed at baseline and at the end of each crossover period. Significantly more patients receiving pilocarpine than dorzolamide reported adverse experiences and discontinued the drug because of these adverse experiences. Similarly, patients reported more interference with their daily life because of side effects and activity limitations when receiving pilocarpine. Vision difficulties, accommodation difficulties, and brow ache were reported more often and were considered more bothersome by patients receiving pilocarpine. Bitter/unusual taste was reported more frequently and was considered more bothersome by patients receiving dorzolamide. Patients also reported missing fewer doses and were more satisfied with their medication when receiving dorzolamide. All of these changes were considered statistically significant. IOP control was not significantly different with either dorzolamide or pilocarpine. However, patients experienced a significant worsening of the mean defect of automated visual field examinations when receiving pilocarpine. At the end of the study, among patients with a preference, dorzolamide was preferred to pilocarpine by a ratio of more than 9:1. Overall, 81.9% of patients preferred dorzolamide. Thus dorzolamide demonstrated better tolerability and less adverse impact on daily life than pilocarpine.