Objective: To examine the outcomes of combination antievascular endothelial growth factor (VEGF) and photodynamic therapy (PDT) for the treatment of neovascular age-related macular degeneration (AMD) refractory to anti-VEGF monotherapy. Design: Retrospective, interventional case series. Participants: Twenty-six eyes of 26 patients treated with anti-VEGF monotherapy for neovascular AMD with persistent subretinal or intraretinal fluid after at least 3 anti-VEGF injections in the 7 months before combination treatment. Intervention: Combination anti-VEGF treatment and PDT. Main Outcome Measures: Visual acuity at 1 or 2, 3, and 6 months and central retinal thickness at 1 or 2, 3, and 6 months. Secondary outcome measures were change in number of fluid-free visits and interval between treatments in the 7 months before and 6 months after combination therapy. Results: Statistically significant improvements in logarithm of the minimum angle of resolution visual acuities were present at 1 month (P = 0.01) and 3 months (P = 0.01). Significant decreases in central subfield retinal thickness on optic coherence tomography (OCT) were seen at 1 month (P = 4 x 10(-5)), 3 months (P = 3 x 10(-4)), and 6 months (P = 4 x 10(-5)) as compared with precombination treatment OCT scans. The percentage of patient visits with no subretinal fluid increased from 0.5% to 41% after the initiation of combination therapy (P = 1 x 10(-5)). The interval between treatments increased from once every 1.6 months in the 7 months before combination treatment to once every 2.7 months in the 6 months after combination treatment (P = 0.002). No ocular complications attributable to PDT were seen. Conclusions: Rescue therapy with the combination of anti-VEGF and PDT in eyes that have failed anti-VEGF monotherapy resulted in a mean improvement in vision, a decreased central subfield retinal thickness, and an increase in fluid-free intervals.