Purpose: To assess the effect of preservative-free dorzolamidetimolol on nonvisual symptoms and intraocular pressure (IOP) in newly diagnosed and untreated patients with open-angle glaucoma or ocular hypertension. Methods: This was a prospective, 8-week, open-label, Canadian multicenter study. All patients were treated with preservative-free dorzolamidetimolol formulation. The primary outcome was the change in the nonvisual symptom score of the Glaucoma Symptom Scale (GSS-SYMP-6) from baseline to 8 weeks. Secondary effectiveness outcome measures were absolute and percent changes in IOP from baseline to 4 and 8 weeks. Results: One hundred and seventy-eight patients were enrolled. Mean (SD) age was 65.6 (12.1) years and 90 (50.6%) were females. There were 92 patients diagnosed with open-angle glaucoma, 62 with ocular hypertension, and 23 with both diseases (diagnosis was missing for one patient). The mean (SD) GSS-SYMP-6 score increased from 73.6 (21.8) at baseline to 76.1 (20.7) at 8 weeks (P = 0.097). Mean (SD) IOP significantly decreased by 11.7 (5.1) mmHg at 4 weeks (P < 0.001) and by 11.5 (5.3) mmHg at 8 weeks (P < 0.001), representing reductions of 38.5% (P < 0.001) and 38.0% (P < 0.001), respectively. Conclusion: Preservative-free dorzolamidetimolol does not increase eye discomfort while significantly reducing IOP in patients with open-angle glaucoma or ocular-hypertension.