Background <p>The main objective was to evaluate the efficacy and safety of anti-VEGF Brolucizumab injection in vitrectomised eyes for post-vitrectomy recalcitrant macular edema in patients with nAMD/ PCV and recalcitrant diabetic macular edemas as per pro-re-nata protocol.</p> Patients and methods <p>A prospective, multi-centric non-randomised interventional study was performed where intravitreal injection of Brolucizumab was administered for post-vitrectomy recalcitrant macular edema as per pro-re-nata protocol. Vitrectomy was performed for sub-macular haemorrhage (Group A) and recalcitrant diabetic macular oedema (Group B).</p> Main outcomes measured <p>Pre- and post-injection BCVA and Central Foveal Thickness (CFT) were noted at 4, 12, 24, 36, 52, and 76 weeks.</p> Results <p>Eighty-one intravitreal injections of Brolucizumab were given in 51 eyes. The BCVA improved from pre-injection LogMAR 0.80 ± 0.32 to 6-month post-injection 0.65 ± 0.23 (Group A, p-value &lt; 0.001, 95% CI) and LogMAR 0.70 ± 0.37 to 0.60 ± 0.34 (Group B, <i>p</i> = 0.378, 95% CI). Significant reduction in CFT noted from pre-injection 367.75 ± 124.12 microns to 6-month post-injection 291.09 ± 81.42 micron (A, <i>p</i> = 0.001, 95% CI) and from 468.45 ± 145.69 micron to 342.19 ± 117.91 micron (B, <i>p</i> = 0.002, 95% CI).</p> Conclusion <p>Brolucizumab may have the potential to be durable, effective and safe in vitrectomised eyes in both post-nAMD and diabetic patients.</p>