Purpose To evaluate the effects of aflibercept administered according to a pro re nata (PRN) or Fixed Regimen to patients with neovascular AMD and persistent intraretinal/ subretinal fluid (IRF/SRF) despite three consecutive ranibizumab injections. Methods Patients were switched to aflibercept injection (IVA) administered according to a PRN or to a fixed regimen for 1 year in two different retina centers. At baseline each patient underwent a complete ophthalmologic evaluation, including bestcorrected visual acuity assessment (BCVA ETDRS chart), fluorescein, and indocyanine green angiography and OCT. Results Each group included 36 eyes. After 1 year the PRN group showed BCVA stabilization (63 vs 60 letters, P = 0.33), whereas fixed regimen group showed significant BCVA improvement (68 vs 71, P = 0.008). The median central retinal thickness decreased by 94 μm in the PRN (P = 0.002) and by 148 μm in the fixed regimen group (P ≤ 0.001). Complete IRF/SRF reabsorption was found in 58% of eyes in the PRN and in 42% of eyes in the fixed regimen group. At 1-year visit, the percentage of eyes with pigment epithelium detachment did not significantly decrease, but a height reduction was recorded in both groups. The median number of IVA was 3.5 in the PRN and 7 in the fixed regimen group. Conclusion The switch to aflibercept with both treatment strategies enabled improvement in morphological parameters and stabilization of visual acuity. BCVA improvement and reduction in vision loss with reduction in retinal thickness, fluid and PED height was achieved with the fixed regimen in previously treated nAMD after 1 year.