Purpose The aim of this study was to evaluate the effects of switching to ranibizumab in patients with neovascular age-related macular degeneration (nAMD) refractory to aflibercept treatment and to identify predictive factors for switch response. Methods A retrospective chart review was conducted including 32 eyes from 26 patients with refractory nAMD, who switched from monthly intravitreal aflibercept treatment (≥ 6 months) to ranibizumab. Outcome measures included changes in visual acuity (VA), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and central retinal thickness (CRT), evaluated at 6 months before switch (T1), at the time of switch (T2), and 3 months post-switch (T3). Results There was an increase in CRT from T1 to T2, which decreased after switch from T2 to T3. Regression analysis of the changes per month observed between time points showed significant differences in PED height ( p = 0.02), SRF ( p = 0.01), and neuroretinal thickness as a measure for IRF ( p = 0.03). No significant change was found for VA. Predictive factors for better switch response included an exacerbation between T1 and T2, thicker measurements at T2, male sex, shorter treatment duration before switch, and fewer preceding injections. No association with preceding switch was found. Conclusion Patients with nAMD refractory to aflibercept benefit from switching to ranibizumab, particularly those whose condition worsened prior to the switch. This may be explained by drug tolerance to aflibercept. Our findings may facilitate making appropriate treatment decisions, potentially improving patient outcomes.