Two hundred thirteen patients participated in the Fluorouracil Filtering Surgery Study, a randomized clinical trial, to determine the efficacy and safety of subconjunctivally injected 5-fluorouracil after filtering surgery in eyes with poor prognoses. Twenty-eight (27%) of the 105 eyes in the 5-fluorouracil group and 54 (50%) of the 108 eyes in the standard group were classified as failures, defined by reoperation for control of intraocular pressure during the first year or an intraocular pressure greater than 21 mm Hg at the one-year visit (P = .0007, Mantel-Haenszel chi-square). Corneal epithelial toxicity and transient visual acuity loss were more common in the 5-fluorouracil group (P less than .001, chi-square); however, the visual acuities and the mean visual field sensitivities were not significantly different at one year. We recommend the use of subconjunctivally injected 5-fluorouracil after trabeculectomy in eyes with uncontrolled glaucoma and poor prognoses, specifically after previous cataract extraction or unsuccessful filtering surgery.