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Purpose: To compare the effectiveness of brinzolamide 1% (Azopt®) and brimonidine 0.2% (Alphagan®) with a placebo in preventing an early increase in intraocular pressure (IOP) after phacoemulsification.Setting: Department of Ophthalmology, Baskent University, School of Medicine, Ankara, Turkey.Methods: In this prospective double-masked study, 90 eyes of 90 patients having clear corneal phacoemulsification were randomly divided into 3 groups of 30 eyes each. One hour before surgery, 1 group received 1 drop of brinzolamide 1%, another received 1 drop of brimonidine 0.2%, and the third received 1 drop of a balanced saline solution (placebo). The IOP was measured preoperatively and 3 and 16 to 20 hours postoperatively.Results: Three hours postoperatively, the mean IOP increased by 4.2 mm Hg ± 7.0 (SD), 3.2 ± 6.4 mm Hg, and 5.3 ± 4.2 mm Hg in the brinzolamide, brimonidine, and placebo groups, respectively. The IOP increase from baseline was significant in all 3 groups (all P<.01), with no difference between the groups (P>.05). The change in IOP at 16 to 20 hours was 0.2 ± 2.8 mm Hg, 0.2 ± 2.4 mm Hg, and –0.8 ± 2.4 mm Hg, respectively. The changes were not significant compared to baseline (all P>.05). Six eyes (20%) in the brinzolamide group, 5 eyes (16.7%) in the brimonidine group, and 7 eyes (23.3%) in the placebo group had an IOP higher than 25 mm Hg 3 hours postoperatively; the difference between groups was not significant (P = .8).Conclusion: Prophylactic use of 1 drop of brinzolamide or brimonidine was not more effective than a placebo in controlling early postoperative IOP elevations after clear corneal phacoemulsification. [Copyright &y& Elsevier]