Purpose: To describe the use of intra-arterial tissue plasminogen activator (tPA) to treat central retinal artery occlusion (CRAO). Methods: A case and its findings were analyzed. Results: A 45-year-old man diagnosed with a CRAO and had cerebral angiography and treatment with intra-arterial tPA. After treatment, follow-up included optical coherence tomography (OCT), fundus photography, fluorescein angiography, and OCT angiography. The visual acuity (VA) improved from hand motions to 20/30 immediately after fibrinolysis. A vascular occlusion event the next day resulted in a decrease in VA to 20/400. After initiation of dual antiplatelet therapy, the patient’s VA improved to 20/20. As the retina recovered, the evolution of retinal ischemic changes to a finding similar to paracentral acute middle maculopathy was seen on imaging. Conclusions: This is the first report describing a patient safely started on dual antiplatelet therapy that led to vision improvement after initial treatment with intra-arterial tPA for a CRAO resulted in recurrent vision loss.