BACKGROUND: In patients with unilateral visual loss related to age-related macular disease, the risk of visual loss in the second eye is documented as being between 7% and 10% per year. The risk is uncertain in those with good vision with each eye and bilateral macular drusen. METHODS: In a prospective study, 126 patients with bilateral drusen were reviewed annually for up to 3 years. Serial fundus photographs and fluorescein angiograms were analyzed independently by two readers in a masked fashion using a standardized grading scheme, including size, number, density, and fluorescence angiographic behavior of drusen. RESULTS: New lesions occurred in one or both eyes of 17 (13.5%) of the 126 patients. The cumulative incidence of exudative or nonexudative lesions was 8.55% at 1 year, at 2 years 16.37%, and 23.52% at 3 years for patients older than 65 years of age. Significant risk factors included the degree of confluence of drusen within 1600 microns of the center of the fovea (P = 0.023), focal hyperpigmentation (P = 0.004), slow choroidal filling (P = 0.023), and focal extrafoveal areas of atrophy of the retinal pigment epithelium (P = 0.042). CONCLUSIONS: The results give an estimate for the incidence of complicating lesions in patients with bilateral drusen and identify those features indicating higher than average risk of visual loss.