Background and Objectives:To report the real-life Brolucizumab therapeutical outcomes of treatment-naïve and non-treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) and to analyze the incidence of therapy-related adverse events.Materials and Methods:A total of 56 eyes of 54 patients diagnosed with nAMD were retrospectively evaluated over a 3-month follow-up. Naïve eyes received a 3-month loading phase, whereas non-naïve eyes were treated with one intravitreal injection + ProReNata scheme. The main outcome measures were best-corrected visual acuity (BCVA) and central retinal thickness (CRT) change. In addition, patients were stratified on the basis of fluid accumulation site, whether intra-retinal (IRF), sub-retinal (SRF), or sub-retinal pigmented epithelium (SRPE), to separately assess the eventual BCVA change in each subgroup. Finally, the incidence of ocular adverse events was evaluated.Results:In naïve eyes, a significant improvement of BCVA (LogMar) was observed at all timepoints from baseline (1 month-Mean Difference (MD): −0.13; 2 months MD: −0.17; 3 months MD: −0.24). In non-naïve eyes, a significant mean change was observed at all timepoints, with the exception of 1-month follow-up (2 months MD: −0.08; 3 months MD: −0.05). CRT significantly changed in both groups at all timepoints at a similar pace within the first two months, with naïve eyes displaying a larger overall thickness decrease at the end of the follow-up (Group 1 = MD: −123.91 µm; Group 2 = MD: −110.33 µm). With respect to the location of the edema, a significant BCVA change was observed in naïve patients with fluid in all three sites at the end of the follow-up (SRPE = MD: −0.13 (p= 0.043); SR = MD: −0.15 (p= 0.019); IR = MD: −0.19 (p= 0.041). Non-naïve patients exhibited significant mean BCVA changes only with respect to SR and IR fluid presence (SRPE = MD: −0.13 (p= 0.152); SR = MD: −0.15 (p= 0.007); IR = MD: −0.06 (p= 0.011). One naïve patient experienced acute-onset anterior and intermediate uveitis which completely resolved after therapy.Conclusions:Brolucizumab was demonstrated to be a safe and efficient alternative in improving both the anatomical and functional parameters of eyes with nAMD in this small, uncontrolled, series of patients.