Objective To assess the results of surgical excision of subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). Design Retrospective, interventional, noncomparative case series. Participants and intervention Sixty-four consecutive patients undergoing surgical removal of AMD-related subfoveal CNV were studied. The surgical method included a small retinotomy, subretinal tissue plasminogen activator (t-PA), perfluoro-n-octane, and air-fluid exchange. Main outcome measures Final visual acuity was the main outcome measure; surgical complications and recurrence rates were also assessed. Results Preoperative visual acuity ranged from 20/100 to 1/200, with a mean of 20/400. Average follow-up was 19 months. The best acuity achieved after surgery ranged from 20/20 to hand motions, with a mean of 20/200. Final visual acuity ranged from 20/50 to light perception, with a mean of 20/400. Final acuity was improved 3 or more lines in 19 eyes (30%) (median, 5 lines), stable in 27 eyes (42%), and 3 or more lines worse in 18 eyes (28%) (median, 4 lines). Factors associated with greater visual improvement included poorer initial acuity, larger CNV size, and smaller subretinal hemorrhage. Analysis of groups similar to Macular Photocoagulation Study subgroups A through D showed an average improvement of 1 line for group C (visual acuity, 20/200 or worse; CNV larger than 2 disc areas). Other preoperative, intraoperative, and postoperative factors, including recurrence and retinal detachment, did not have a significant effect on final visual outcome. Conclusions After surgical excision of AMD-related subfoveal CNV, vision improved or stabilized in the majority of patients. Surgery may be of greatest value for patients with poorer vision, larger subfoveal CNV, and minimal hemorrhage. Further evaluation of this technique should be accomplished via completion of a controlled, randomized multicenter study.