To assess the short-term safety and efficacy of treating subfoveal choroidal neovascularization (CNV) with external beam radiation delivered in 5 × 4 Gy fractions among patients having age-related macular degeneration (AMD). A multicenter prospective randomized controlled pilot study. Eighty-eight patients were enrolled through 10 sites and were randomized to radiotherapy (20 Gy delivered in 5 daily fractions of 4 Gy each; 6 MV N = 41) or no radiotherapy (sham radiotherapy N = 22 or observation N = 25). Eligibility criteria included visual acuity of at least 20/320 and subfoveal CNV not amenable to treatment. Randomization was stratified by lesion type (new or recurrent CNV) and blood (<50% or ≥50% of the lesion N = 13). The primary outcome measure was loss of ≥3 lines of visual acuity. Secondary outcome measures were angiographic response and side effects. At baseline, patient and ocular characteristics were similar between treatment groups. At six months, 9 radiated eyes (26%) and 17 eyes not radiated (49%) lost ≥3 lines of visual acuity ( P = .04; stratified χ 2 test). At 12 months, 13 radiated eyes (42%) and 9 observed eyes (49%) lost ≥3 visual acuity lines ( P = .60). The radiated group demonstrated smaller lesions and less fibrosis than the nonradiated group ( P = .05 and .004, respectively) at 12 months. Radiation-induced complications were not observed except for one radiated eye with numerous cotton wool spots and possible radiation retinopathy. External beam radiation at 5 × 4 Gy may have a modest and short-lived (six month) benefit in preserving visual acuity.