Ranibizumab and bevacizumab were compared in a 2-year trial for neovascular age-related macular degeneration (AMD). Patients were randomized to four treatment groups: ranibizumab or bevacizumab with monthly or as-needed dosing. After one year, patients initially assigned to monthly treatment were randomly reassigned to either monthly or as-needed treatment. Visual acuity improvements were similar between the two drugs, with no significant difference in mean gain (bevacizumab-ranibizumab difference: -1.4 letters; 95% CI: [-3.7, 0.8]; p=0.21). Monthly treatment resulted in greater visual acuity gain than as-needed treatment (difference: -2.4 letters; CI: [-4.8, -0.1]; p=0.046). The proportion of patients without fluid was higher in the ranibizumab monthly group (45.5%) compared to the bevacizumab as-needed group (13.9%). Switching from monthly to as-needed treatment resulted in a greater decrease in vision (-2.2 letters, p=0.03) and a lower proportion without fluid (-19%, p<0.0001). Rates of death and arteriothrombotic events were similar between the two drugs. Bevacizumab was associated with a higher proportion of serious adverse events (39.9% vs. 31.7%; adjusted risk ratio 1.30; CI [1.07, 1.57]; p=0.009). The study found that ranibizumab and bevacizumab had similar effects on visual acuity over two years. As-needed treatment resulted in less visual acuity gain compared to monthly treatment, whether initiated at enrollment or after one year of monthly treatment. There were no differences between the drugs in rates of death or arteriothrombotic events. The higher rates of serious adverse events with bevacizumab remain uncertain due to the lack of specificity to conditions associated with VEGF inhibition. The results suggest that both drugs are effective, but bevacizumab may carry a higher risk of serious adverse events. The choice of drug and dosing regimen should balance the comparable effects on vision, the possibility of true differences in adverse events, and the significant cost difference between the two drugs.Ranibizumab and bevacizumab were compared in a 2-year trial for neovascular age-related macular degeneration (AMD). Patients were randomized to four treatment groups: ranibizumab or bevacizumab with monthly or as-needed dosing. After one year, patients initially assigned to monthly treatment were randomly reassigned to either monthly or as-needed treatment. Visual acuity improvements were similar between the two drugs, with no significant difference in mean gain (bevacizumab-ranibizumab difference: -1.4 letters; 95% CI: [-3.7, 0.8]; p=0.21). Monthly treatment resulted in greater visual acuity gain than as-needed treatment (difference: -2.4 letters; CI: [-4.8, -0.1]; p=0.046). The proportion of patients without fluid was higher in the ranibizumab monthly group (45.5%) compared to the bevacizumab as-needed group (13.9%). Switching from monthly to as-needed treatment resulted in a greater decrease in vision (-2.2 letters, p=0.03) and a lower proportion without fluid (-19%, p<0.0001). Rates of death and arteriothrombotic events were similar between the two drugs. Bevacizumab was associated with a higher proportion of serious adverse events (39.9% vs. 31.7%; adjusted risk ratio 1.30; CI [1.07, 1.57]; p=0.009). The study found that ranibizumab and bevacizumab had similar effects on visual acuity over two years. As-needed treatment resulted in less visual acuity gain compared to monthly treatment, whether initiated at enrollment or after one year of monthly treatment. There were no differences between the drugs in rates of death or arteriothrombotic events. The higher rates of serious adverse events with bevacizumab remain uncertain due to the lack of specificity to conditions associated with VEGF inhibition. The results suggest that both drugs are effective, but bevacizumab may carry a higher risk of serious adverse events. The choice of drug and dosing regimen should balance the comparable effects on vision, the possibility of true differences in adverse events, and the significant cost difference between the two drugs.