The efficacy of twice-daily treatment with 0.5% apraclonidine drops was evaluated retrospectively in patients with uncontrolled advanced glaucoma who were poor surgical candidates and on maximal tolerated medical therapy. Fifty-eight eyes of 48 patients were treated chronically with apraclonidine and had no additional concurrent pharmacologic or laser or surgical manipulations. The mean baseline intraocular pressure was 30.0 $pM 1.1 mm Hg. The mean percentage of decrease in intraocular pressure in the various diagnostic groups ranged from 13.6 to 30.8% at the first follow-up visit and from 23.2 to 37.3% at peak reduction. Eighty-one percent of the patients with baseline intraocular pressure >21 mm Hg showed ≤5 mm Hg decrease, and 75% showed a reduction ≤20%; 48% of the latter sustained the ≤20% response for at least 4 weeks and 43% for at least 8 weeks. Primary and secondary glaucomas did not differ in magnitude and duration of response, but developmental and congenital glaucomas responded less well. Intermediate or long-term apraclonidine therapy may be a reasonable alternative in selected glaucoma patients.