To investigate differences in baseline characteristics, outcomes, and metrics of swept-source optical coherence tomography (SS-OCT) angiography between drusen-associated neovascular age-related macular degeneration (nAMD) vs pachychoroid neovasculopathy. This prospective cohort study enrolled 1 eye per patient with treatment-naïve nAMD or pachychoroid neovasculopathy who underwent 3 monthly bevacizumab injections followed by a treat-and-extend regimen for 12 months or longer. Eligible patients were classified into 2 groups: those with drusen-associated nAMD and those with pachychoroid neovasculopathy. Drusen-associated nAMD refers to macular neovascularization (MNV) or polypoidal lesions surrounded by subretinal drusenoid deposits or soft drusen 63 μm or larger in diameter. The outcomes were collected at baseline, 6 months, and 12 months. Patients with drusen-bordering MNV (51 cases) were older (69.6 years vs 64.2 years) and had a smaller ratio of low-density to high-density lipoprotein cholesterol (1.85 vs 2.14), longer daily sleep hours (7.03 hours vs 6.07 hours), a smaller proportion of patients with a history of central serous chorioretinopathy (CSCR) (0% vs 12.5%), and smaller baseline central choroidal volume compared with those with pachychoroid neovasculopathy (57 cases). At 12 months, eyes with drusen exhibited a lower choroidal vascularity index, larger foveal thickness (327 µm vs 273 µm), and more antivascular endothelial growth factor injections per year (7.0 vs 5.2) compared with eyes with pachychoroid neovasculopathy. Regarding secondary outcomes, a closed-circuit vascular pattern was associated with persistent retinal fluid at study completion. Patients with pachychoroid neovasculopathy appear to carry some systemic risk factors for CSCR, whereas patients with drusen-related nAMD had inferior responses to bevacizumab monotherapy and greater choriocapillaris hypoperfusion (characterized by thinner choroidal volume and lower choroidal vascularity index values).