Objective Ketorolac tromethamine 0.5% and diclofenac sodium 0.1% ophthalmic solutions are approved for use by the U.S. Food and Drug Administration to avoid excessive postoperative inflammation after cataract surgery and implantation of an intraocular lens. This study compares the efficacy and toxicity of these nonsteroidal anti-inflammatory drugs for the first time. Design Randomized, double-masked, prospective clinical trial. Participants A total of 120 patients assigned in equal numbers to 1 of the 2 treatment regimens. Intervention Treatment with either ketorolac 0.5% or diclofenac 0.1% ophthalmic solutions instilled four times daily for 30 days beginning the first postoperative day after surgery. Main outcome measures Objective (Kowa FC 1000 laser cell and flare meter) and subjective (slit-lamp biomicroscope) measurements of inflammation and toxicity were made and compared at three separate postoperative visits. Results The anti-inflammatory effects of the two treatment regimens were not statistically different at any of the postoperative visits. Patients tolerated both treatments equally well. Conclusions This study shows diclofenac sodium 0.1% and ketorolac tromethamine 0.5% ophthalmic solutions are equally effective and safe for the control of postoperative inflammation after uncomplicated cataract surgery performed by phacoemulsification followed by the implantation of a foldable intraocular lens.