OBJECTIVE This study aimed to describe characteristics of choroidal neovascularization (CNV) that developed in high-risk eyes of patients with age-related macular degeneration (AMD) enrolled in the Choroidal Neovascularization Prevention Trial (CNVPT). METHODS Consecutive case series among patients enrolled in a multicenter, randomized controlled trial. METHODS Eighteen eyes of 18 patients who developed exudative AMD were studied from among 156 patients with large drusen enrolled in the Bilateral Drusen Study and 120 patients having one eye with exudative AMD and the other eye with large drusen enrolled in the Fellow Eye Study. The CNVPT Fellow Eye Study provided 12 eyes (10, treatment group; 2, control group), and the CNVPT Bilateral Drusen Study contributed 6 eyes (4, treatment group; 2, control group). METHODS The CNVPT Reading Center assessment and grading of patients with CNV and other exudative complications was reviewed. METHODS Onset of CNV, laser intensity for treated eyes, classification of lesion components, size of lesion, location of lesion, foveal involvement, and change in visual acuity were measured. RESULTS Eighteen eyes showed onset of CNV between 2 and 21 months after enrollment. In comparison with the CNVPT Laser Standard Intensity, variations in laser treatment intensity (6 eyes graded less than standard intensity and 8 eyes graded standard intensity) were not associated with CNV events. Seventeen of 18 eyes showed occult CNV in whole or in part, and only 1 eye manifested purely classic CNV. The median size range was 2 to 3.5 disc areas. Among the 14 treated eyes that developed exudative lesions, 7 showed subfoveal involvement and 13 had CNV associated with the region of treatment. At the time of the CNV event, 9 of 18 eyes showed greater than a 2-line loss of vision from baseline while the remaining eyes were stable. CONCLUSIONS Preliminary data show that visually significant exudative manifestations of AMD may develop in patients with high-risk drusen who undergo macular laser photocoagulation. The CNV lesions typically are occult, often subfoveal, and associated with the region of treatment. Longer follow-up is warranted.