A five-year (1979–1984) prospective, randomized, controlled, collaborative study was performed by 27 experienced vitrectomy surgeons in 15 medical centers on 136 surgically aphakic eyes without lens implants but with vitreous adherent to the corneoscleral wound and with chronic aphakic cystoid macular edema (ACME). One hundred fifteen eyes completed the entire course of investigation. The purpose of the study was twofold: to determine the effectiveness of vitrectomy in eliminating established ACME and to determine the natural history of this condition. Following criteria contained within the study protocol, 68 eyes were randomized to surgery (RAN-S) or control (RAN-C), and 47 eyes were observed in the long-term observation group (LTO). Twenty-one eyes were eliminated from the investigation for reasons stated in the text. The RAN-S group proved to have a significantly better visual course than the RAN-C group (P = <0.01). An analysis of the LTO group revealed that if central vision did not decline to a level of 20/80 or worse, 27% of the eyes had a chance of spontaneously improving to a level of 20/50 or better. However, if central vision declines to or beyond this point, spontaneous visual improvement to 20/50 or better only occurred in 8% of eyes. Also reported are other important clinical findings such as the role of systemic diseases in ACME, the incidence of vitreous traction on the macula, prognostic value of pre-surgical medical therapy, a comparison of limbal versus pars plana surgical approach, the timing of surgery, and the effectiveness of fluorescein angiography as an objective monitor of visual function.