Purpose: To describe a case of allergic reaction to intravitreal (IVT) injection of antivascular endothelial growth factor (anti-VEGF) medications in patients with alpha-gal syndrome. Methods: A single case was evaluated. Results: A 57-year-old woman with a known diagnosis of alpha-gal syndrome was evaluated. Clinical presentation, prior treatment history, and response to different anti-VEGF agents were reviewed. The patient presented with worsening vision in her right eye due to a subfoveal choroidal neovascular membrane secondary to neovascular age-related macular degeneration. She had experienced a systemic allergic reaction following an IVT injection of bevacizumab but subsequently tolerated ranibizumab without any adverse effects, resulting in improvement in her vision. Conclusions: Bevacizumab, aflibercept, and faricimab are recombinant immunoglobulins produced by DNA technology in Chinese hamster ovary cells, which may contain galactose-α-1,3-galactose (alpha-gal), a potential allergen for patients with alpha-gal syndrome. Patients with alpha-gal syndrome may develop allergic reactions to certain IVT anti-VEGF agents derived from mammalian expression systems. Ranibizumab, produced using an Escherichia coli expression and lacking alpha-gal, seems to be a safe and effective option for patients with alpha-gal syndrome requiring IVT anti-VEGF therapy.