Purpose This randomized, masked, prospective study was conducted to compare the outcome of filtering surgery using doses of 0.2 mg/cc or 0.4 mg/cc of mitomycin C (MMC) in eyes that were at higher risk from previous conjunctival incisional surgery. Methods Eyes of 50 consecutive patients with primary open-angle, pseudoexfoliation, or pigmentary glaucoma requiring trabeculectomy who had previously undergone either limbal cataract surgery or trabeculectomy were enrolled. Patients received an intraoperative dose of either 0.2 or 0.4 mg/cc MMC for 2 minutes (n = 25 in each study group). Intraocular pressure (IOP), logMAR visual acuity, and complications were monitored at regular intervals for 1 year. Unpaired student t tests were used to compare percent decrease in IOP in both study groups at each interval. Results The percent decrease in IOP was not significantly different between groups at 1 day, 1 week, 1 month, 3 months, 6 months, or 1 year after surgery. LogMAR visual acuity was not significantly different between groups at 1 month, 6 months, or 1 year. Treatment failure occurred in seven patients in the 0.2 mg/cc group (28%) and seven patients in the 0.4 mg/cc group (29.2%). Postoperative hypotony, choroidal effusions and hemorrhages, and wound leaks occurred in both groups, but occurred more often in the group receiving 0.4 mg/cc MMC. Conclusion Filtering surgery performed on higher risk eyes was as effective using a lower dose (0.2 mg/cc) of MMC as that using a higher dose (0.4 mg/cc). Incidence of complications and treatment failures was slightly higher in the group receiving high-dose MMC.