OBJECTIVE To compare the bioavailability and pupillary effect of flurbiprofen and indomethacin during phacoemulsification and intraocular lens implantation. METHODS Gimbel Eye Centre, Calgary, Alberta, Canada. METHODS In this prospective, randomized, double-masked study, 236 patients had cataract extraction by phacoemulsification and posterior chamber intraocular lens implantation. They received topical flurbiprofen 0.03% solution or indomethacin 1% suspension applied every 15 minutes for 60 to 75 minutes before surgery. An aqueous humor sample (100 microL) was taken immediately before the corneal incision was made. Pupil diameters (horizontal and vertical) were measured before aqueous humor sampling, after phacoemulsification, after irrigation and aspiration (I/A), and after acetylcholine instillation. RESULTS Mean concentration of flurbiprofen and indomethacin in the aqueous humor was 59.8 ng/mL and 90.2 ng/mL, respectively (P < .001). The percentage of dose detected in the aqueous humor was 4.38% in the flurbiprofen group and 0.21% in the indomethacin group (P < .001). Pupil diameters were 7.2 and 7.3 mm presurgery and 7.0 and 7.0 mm after I/A in the flurbiprofen and indomethacin groups, respectively (P > .05). No adverse events were reported in either group. CONCLUSIONS Although the absolute concentration of indomethacin was higher, the percentage of dose detected in the aqueous humor was 20 times greater in the flurbiprofen than in the indomethacin group. Flurbiprofen is absorbed 20 times more readily than indomethacin. Both drugs were equally effective in preventing miosis during cataract surgery.