The aim of this study was to evaluate the early response of aflibercept as first-line therapy in treatment-naive patients with newly diagnosed choroidal neovascularization (CNV) in age-related macular degeneration (AMD). An analysis of 35 eyes (35 patients, 28 female, 7 male) with treatment-naive active CNV was undertaken. Lesion activity was determined based on fluorescein angiography, clinical and optical coherence tomography (OCT) findings, including the presence of sub-, intraretinal fluid, retinal pigment epithelial (RPE) detachment and hemorrhage. Logarithm of the minimum angle of resolution (LogMAR) charts were used for testing best corrected or best available visual acuity (BCVA). Treatment response was evaluated based on changes in BCVA and lesion activity. Classic or predominantly classic CNV was diagnosed in 7 eyes (20.0%), occult or minimally classic in 21 eyes (60.0%), retinal angiomatous proliferation in 5 eyes (14.3%) and polypoidal choroidal vasculopathy in 2 eyes (5.7%). Lesion activity was evaluated as unchanged in only one eye. In all other eyes, a definite treatment response was observed with complete resolution of fluid in 20 eyes after a single injection. Three eyes did not show improved sub-RPE fluid with smaller pigment epithelial detachments. A rip of the RPE was seen in 3 eyes. All patients maintained vision, 7 patients (7 eyes) gained >15 letters from baseline to month 2 follow-up, of whom 4 reached this level of visual acuity after one injection. The visual acuity gains in this study were maintained through 6 months. There seems to be a rapid treatment response to aflibercept independent of the underlying CNV. Aflibercept may be beneficial even in eyes with large pigment epithelial detachments due to exudative AMD.