This case report describes full-thickness macular hole formation after intravitreal aflibercept injections for the treatment of macular neovascularization in neovascular age-related macular degeneration (AMD). Only limited case reports and case series have reported this possible adverse event after aflibercept injection. Possible mechanisms leading to the formation of a macular hole subsequent to intravitreal injection are focal tractional forces on the vitreoretinal interface due to globe deformation during needle insertion, vitreous syneresis, and vitreous incarceration at the injection site, and tangential shearing forces on the posterior surface of the retina due to contraction and rapid volume reduction of the neovascular membrane or a decrease in intra- or subretinal fluid. Furthermore, some reports suggest a toxic effect of the anti-vascular endothelial growth factor agent on a previously compromised retina as etiological factor. Macular hole formation may thus represent a rare adverse event of intravitreal aflibercept injection in patients with neovascular AMD, and it should be included in the differential diagnosis of post-injectional visual loss.