We report the preliminary 3-month outcome of a multicenter randomized trial of cryotherapy for treatment of retinopathy of prematurity (ROP). Transscleral cryotherapy to the avascular retina was applied to one randomly selected eye when there was threshold disease (defined as five or more contiguous or eight cumulative 30° sectors [clock hours] of stage 3 ROP in zone 1 or 2 in the presence of 'plus' disease). An unfavorable outcome was defined as posterior retinal detachment, retinal fold involving the macula, or retrolental tissue. At this writing, 172 infants had been examined 3 months after randomization. An unfavorable outcome was significantly less frequent in the eyes undergoing cryotherapy (21.8%) compared with the untreated eyes (43%). While the surgery was stressful, no unexpected complications occurred during or following treatment. These data support the efficacy of cryotherapy in reducing by approximately one half the risk of unfavorable retinal outcome from threshold ROP.