Purpose: To examine the efficacy and safety of a new gel formulation loteprednol etabonate 0.5% in the treatment of inflammation and pain after cataract surgery. Setting: Seventeen United States clinical sites. Design: Prospective double-masked parallel-group study. Methods: Patients with anterior chamber cell (ACC) grade 2 or higher after cataract surgery were randomized to loteprednol etabonate 0.5% gel or vehicle 4 times a day for 14 days. Primary outcome measures included the proportion of patients with complete resolution of ACC and grade 0 (no) pain on postoperative day 8. Safety measures included adverse events, intraocular pressure (IOP), visual acuity, biomicroscopy and funduscopy findings, and tolerability (ocular symptoms and drop comfort). Results: The intent-to-treat population included 406 patients (203 per treatment). On day 8, 30.5% of patients in the loteprednol etabonate group and 16.3% of patients in the vehicle group had complete resolution of ACC, whereas 72.9% and 41.9%, respectively, had grade 0 pain (both P<.001). Significant treatment differences for complete resolution of ACC and grade 0 pain favoring loteprednol etabonate were also found on day 15 and day 18. One patient in each treatment group had a significant increase in IOP (≥10 mm Hg). Analyses of pain, photophobia, and tearing favored loteprednol etabonate at different time points beginning on day 3. More than 85% of patients in each treatment group reported no discomfort on drop instillation. Conclusion: Loteprednol etabonate gel 0.5% was efficacious and safe in treating postoperative inflammation and pain. Financial Disclosure: Dr. Rajpal is a consultant to Bausch & Lomb, Inc., Allergan, Inc., and Alcon Laboratories, Inc. Dr. Siou-Mermet and Ms. Erb are employees of Bausch & Lomb, Inc. Dr. Roel has no financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]