This study deals with the role of the topical administration of dorzolamide eyedrops on the oxidative/antioxidant status of aqueous humor in patients with primary open angle glaucoma (POAG). A case-control study including 130 patients distributed into three groups was carried out: 1) patients with POAG without dorzolamide instillation administration (GG; n=34); 2) patients with POAG with dorzolamide (DG; n=36); and 3) subjects with cataracts (comparative group, CG; n=60). Oxidative activity was measured in the aqueous humor by malondialdehyde determination by the thiobarbituric acid reactive substances assay. Antioxidant status was assessed in the aqueous humor samples by measuring the superoxide dismutase activity and the total antioxidant status. Oxidative activity was significantly higher in both glaucoma groups than in the cataracts group (GG vs CG, p=3.68 E-34; DG vs CG, p=5.11 E-45) and was significantly higher in GG than in DG (p=0.0034). SOD activity was significantly higher in both glaucoma groups than in the cataracts group (GG vs CG, p=1.08 E-14; DG vs CG, p=3.70 E-22), and was significantly higher in GG than in DG (p=0.018). Finally, total antioxidant status was significantly decreased in both glaucoma groups compared with the cataracts group (GG vs CG, p=2.51 E-12; DG vs CG, p=5.06 E-05), and was more significantly decreased in GG than in DG (p=9.23 E-07). Topical administration of dorzolamide colirium diminishes oxidative stress in patients with glaucoma.