Various doses of a new topical nonsteroidal anti-inflammatory agent, diclofenac sodium, were tested against prednisolone sodium phosphate in a randomized double-masked study to determine comparative efficacy and safety regarding the reduction of postsurgical ocular inflammation. Inflammation was assessed by measuring fluorescein leakage into the anterior chamber using fluorophotometry techniques. Increased leakage in each patient's operated-on eye compared with the unoperated-on control eye was attributed to a breakdown in the blood-aqueous barrier caused by the cataract surgery. Elimination or significant reduction of fluorescein leakage within a treatment group constituted increased efficacy in controlling inflammation. A total of 124 cases were analyzed. There were no preoperative differences among groups in fluorescein leakage. At 1 week after surgery, all three diclofenac groups had significantly less fluorescein leakage compared with the prednisolone group. Mean percent increases were 56% to 118% in diclofenac groups vs 324% in the prednisolone group. No differences among diclofenac concentrations were detected. The differences between prednisolone and diclofenac were also present, although of lesser magnitude, at 3 weeks. This demonstration of increased efficacy of the nonsteroidal anti-inflammatory agent vs prednisolone is promising given the known side effects of ocular steroids.