OBJECTIVE Retinal arterial occlusion is one of the most dramatic problems faced by ophthalmologists because of its sudden onset and the severe consequences it may have on the visual system. In this study, local intra-arterial fibrinolysis (LIF) using recombinant tissue plasminogen activator (rTPA) as a new technique for the treatment of retinal arterial occlusion was investigated. METHODS Retrospective, noncomparative case series. METHODS Strict inclusion and exclusion criteria were used to select patients for treatment. Fifty-three patients with central retinal artery occlusion (n = 46) or branch retinal arterial occlusion (n = 7) were enrolled. METHODS For a maximum of 3 hours, 10- to 20-mg rTPA per hour in 50-ml sodium chloride was infused transfemorally by catheterization of the ophthalmic artery with a variable stiffness microcatheter. METHODS The best-corrected visual acuity for distance by an 18-line logarithmic table was measured on admission, at 24 hours, and at 3 months after intervention. RESULTS At 3 months, visual acuity had improved in 35 (66%) of 53 patients. Twenty-five (47.2%) patients showed an improvement of more than 2 lines, and in 10 (18.8%) patients, improvements of 1 to 2 lines were observed. No change in visual acuity occurred in 12 (22.6%) patients, and in 6 (11.3%) patients, the visual acuity deteriorated. The mean occlusion time was 14 hours (range, 3-50 hours). No statistically significant correlation was found between occlusion time and visual outcome (P > 0.22). In two patients, a temporary slight hemiplegia was observed during catheterization, and in one patient, a hypertensive crisis after LIF treatment was observed. CONCLUSIONS The high success rate of LIF using rTPA in patients suffering from retinal arterial occlusion is supposedly due to a causal effect of rTPA on primary platelet-fibrin emboli and secondary thrombi. The local fibrinolytic therapy with rTPA involves little risk for patients selected by strict inclusion and exclusion criteria. It may be used for the treatment of retinal arterial occlusion even later than 8 hours after the acute visual loss. However, a successful outcome of the therapy depends on the prompt referral by well-informed ophthalmologists; a speedy execution of all internal, neurologic, and ophthalmologic diagnostic measures; and a prompt therapy.