Ischemic stroke causes vascular and neuronal tissue deficiencies that could lead to significant functional impairment and/or death. Although progenitor-based vasculogenic cell therapies have shown promise as a potential rescue strategy following ischemic stroke, current approaches face major hurdles. Here we used fibroblasts nanotransfected with Etv2, Foxc2, and Fli1 (EFF), to drive reprogramming-based vasculogenesis, intracranially, as a potential therapy for ischemic stroke. Perfusion analyses suggest that intracranial delivery of EFF-nanotransfected fibroblasts led to a dose-dependent increase in perfusion 14 days post-injection. MRI and behavioral tests revealed ~70% infarct resolution and up to ~90% motor recovery for mice treated with EFF-nanotransfected fibroblasts. Immunohistological analysis confirmed increases in vascularity and neuronal cellularity, as well as reduced glial scar formation in response to treatment with EFF-nanotransfected fibroblasts. Altogether, our results suggest that vasculogenic cell therapies based on nanotransfection-driven (i.e., non-viral) cellular reprogramming represent a promising strategy for the treatment of ischemic stroke.