Medical therapy has been the standard initial treatment for open-angle glaucoma. When some visual field has been lost and maximum tolerated and effective medical therapy does not succeed in controlling the disease, the patient is considered to have advanced glaucoma, and the first of a potential sequence of surgical treatments is usually indicated. Little is known about the long-term course and prognosis of advanced glaucoma or about the long-term effectiveness of sequential surgical treatments in controlling the disease and preventing vision loss and blindness. The Advanced Glaucoma Intervention Study was designed to study, in advanced glaucoma, the long-term clinical course and prognosis, and, in a randomized trial, the comparative outcomes of two sequences of surgical treatments. Toward these goals, 789 eyes in 591 patients were enrolled at 11 clinical centers between 1988 and 1992. Follow-up will continue until 1996. Eyes were randomly assigned to one of two sequences of surgical treatments. One sequence begins with argon laser trabeculoplasty (ALT), is followed by trabeculectomy, an incisional surgical filtering procedure, should ALT fail to control the disease, and by a second trabeculectomy should the first trabeculectomy fail. The other sequence begins with trabeculectomy, is followed by ALT should the trabeculectomy fail, and by a second trabeculectomy should ALT fail. The main outcome of interest is visual function (visual field and visual acuity). Other important outcomes are intraocular pressure, complications of surgery, time to treatment failure, and extent of need for additional medical therapy. We present in this paper the rationale, objectives, design and methods of the study, and the baseline characteristics of study patients and eyes.