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PURPOSE To determine the effects of topical 0.45% ketorolac tromethamine on intraoperative miosis and prostaglandin E2 (PGE2) release during femtosecond laser-assisted cataract surgery. SETTING Seoul St. Mary's Hospital, Seoul, Korea. DESIGN Prospective case series. METHODS The study comprised the following 3 groups: conventional cataract surgery without topical NSAIDs (conventional group); femtosecond laser-assisted cataract surgery with preoperative topical ketorolac tromethamine 0.45% (femtosecond NSAID group), and femtosecond laser-assisted cataract surgery without topical NSAIDs (femtosecond no-NSAID group). To measure the aqueous humor PGE2 concentration, a 100 μL aqueous humor sample was collected from the anterior chamber after femtosecond laser pretreatment. The PGE2 concentration was measured using an enzyme immunoassay. RESULTS Topical ketorolac tromethamine 0.45% led to a significant reduction in intraoperative miosis in the femtosecond NSAID group compared with the femtosecond no-NSAID group (P < .001). Absolute and relative reductions in pupil area in the femtosecond NSAID group were significantly lower than in the femtosecond no-NSAID group (P = .019 and P = .007, respectively). The mean aqueous humor PGE2 concentrations were 893.60 pg/mL ± 843.10 (SD) in the conventional group, 1911.43 ± 1178.63 pg/mL in the femtosecond NSAID group, and 743.63 ± 927.46 pg/mL in the femtosecond no-NSAID group (P < .001, conventional versus femtosecond NSAID and femtosecond NSAID versus femtosecond no NSAID; P > .05, conventional versus femtosecond NSAID). CONCLUSION Preoperative topical ketorolac tromethamine 0.45% reduced miosis induced by femtosecond laser pretreatment and inhibited aqueous humor PGE2 elevation.