Patients who participated in the Fluorouracil Filtering Surgery Study, a clinical trial in which patients were randomly assigned to treatment to determine the efficacy and safety of subconjunctivally injected 5-fluorouracil after filtering surgery in eyes with poor prognoses, were followed up for three years. Treatments in 49 of the 100 eyes in the 5-fluorouracil group and 73 of the 99 eyes (74%) in the standard treatment group were classified as failures, defined by reoperation for control of intraocular pressure or intraocular pressure greater than 21 mm Hg during the first three years postoperatively (P < .001, chi-square). Late-onset leakage of aqueous through the filtering bleb occurred more frequently in the 5-fluorouracil group (seven of 105 eyes, 7%) than in the standard treatment group (none of 108 eyes, 0%) (P = .006, Fisher's exact test). We recommend the use of 5-fluorouracil after trabeculectomy in eyes after previous cataract extraction or unsuccessful filtering surgery. The increased risk of late-onset conjunctival filtering bleb leaks associated with 5-fluorouracil cautions against its routine use in patients with good prognoses.