Purpose: To report the anatomic and functional outcome in patients with severe visual loss after acute massive submacular hemorrhage secondary to retinal arterial macroaneurysm submitted to vitrectomy and subretinal recombinant tissue plasminogen activator injection. Methods: Retrospective, observational, case-series of 4 eyes of 4 patients submitted to pars plana posterior vitrectomy (ppV) combined with internal limiting membrane (ILM) removal and subretinal recombinant tissue plasminogen activator (rtPA-12.5 mg/0.1 ml) injection with dilute (20%) sulfur hexafluoride (SF6) gas in the vitreous cavity of eyes with recent onset (≤7 days) massive macular hemorrhage due to retinal arterial macroaneurysm (RAMA). Optical coherence tomography (OCT) was obtained both at presentation and during follow up. Results: Patients ranged in age from 63 to 78 years and all had systemic arterial hypertension. Visual acuity at presentation ranged from hand motions to count fingers at 50 cm. All eyes showed extensive retinal hemorrhage involving more than two-thirds of macular area. The time between the onset of symptoms and the surgery ranged from 3 to 7 days. After a mean postoperative follow-up of 15.5 ± 5.19 months (range, 10-22 months), all eyes showed visual acuity improvement and final visual acuity ranged from 20/30 to 20/80. All had complete displacement of the subretinal hemorrhage from the fovea after the surgery. OCT images showed neurosensory retina thinning and disruption of the reflective line that represents the junction between inner and outer photoreceptors segments (IS/OS line) beneath the macular area and absence of the external limiting membrane (ELM). Conclusions: ppV associated with subretinal rtPA injection with intravitreal gas seems to be a safe and effective technique to promote visual improvement in patients with multilevel macular hemorrhage secondary to RAMA. Despite functional improvement, OCT images demonstrate that submacular hemorrhage leads to permanent structural damage to the neurosensory retina, especially to the outer photoreceptors layers.