<b><i>Purpose:</i></b> To evaluate outcome predictors of aflibercept in neovascular age-related macular degeneration pretreated with ranibizumab based on a treat-and-extend regimen (TER). <b><i>Methods:</i></b> We performed a retrospective evaluation of 18-month follow-up of 45 consecutive patients with limited response to ranibizumab. <b><i>Results:</i></b> At month 18, mean central retinal thickness and intraretinal fluid (IRF) height were significantly reduced. The recurrence-free treatment interval (RFTI) increased from 7.0 ± 1.8 to 8.5 ± 2.4 weeks (<i>p</i> = 0.01); visual acuity remained stable. At month 18, 58.1% of patients showed a longer RFTI. At month 12, eyes with baseline subretinal fluid (SRF) had a shorter RFTI than those without SRF (<i>p</i> = 0.032). Eyes with baseline IRF showed a longer RFTI than those without IRF (<i>p</i> = 0.037). Baseline hyperreflective foci (HRF) presence indicated improvement in SRF (<i>p</i> = 0.024) and IRF at month 12 (<i>p</i> = 0.049). <b><i>Conclusion:</i></b> Baseline HRF presence predicted better morphological outcome, while SRF predicted a shorter RFTI and IRF a longer RFTI after switching from ranibizumab to aflibercept within a TER.