To report an association between spontaneous subhyaloidal hemorrhage and severe plasminogen activator inhibitor-1 (PAI-1) deficiency. Case report. A 29-year-old woman presented with sudden, painless visual loss to hand motion in her right eye. Ophthalmoscopy showed a massive subhyaloidal hemorrhage. The patients' medical history was negative for cardiovascular risk factors, trauma, infections or bleeding complications. Further investigation into possible causes revealed hyperfibrinolysis secondary to severe PAI-1 deficiency. The non-clearing subhyaloidal hemorrhage was successfully treated by pars plana vitrectomy, and her visual acuity improved to 20/20. When ordering laboratory tests in patients with spontaneous subhyaloidal hemorrhage to rule out fibrinolytic disorders, severe PAI-1 deficiency should be considered in the differential diagnosis. Selective screening may be helpful in identifying ophthalmologic patients with hyperfibrinolysis, especially in young individuals with subhyaloidal hemorrhages in the absence of other recognized risk factors.