We present 2 cases of iatrogenic retinal penetration from intravitreal (IVT) injections in a retrospective noncomparative case series of 2 patients. The first patient, an 81-year-old Caucasian male, developed dense vitreous hemorrhage soon after receiving an IVT bevacizumab injection for macular edema from central retinal vein occlusion. A 25-g vitrectomy 1 week later showed a retinal hole surrounded by fresh hemorrhages in the same quadrant as the IVT injection. The second patient, an 87-years-old male, developed a retinal detachment after 28 injections of anti-VEGF medications for neovascular AMD. A peripheral round hole was observed during vitrectomy without any lattice degeneration in the same quadrant as prior IVT injections. Both eyes were pseudophakic, had normal axial lengths, and received injections without measuring the injection site. Retinal penetration from IVT injections can result in serious sight-threatening complications. Measuring the injection site from the limbus should be part of safe IVT injection technique.