Four patients with Ehlers-Danlos syndrome presented spontaneously with symptomatic direct carotid-cavernous fistulas. Two had previously (2 and 15 years, respectively) had contralateral carotid-cavernous fistulas that were treated with carotid occlusion procedures. The patients' ages at presentation ranged from 19 to 49 years, with a mean of 32 years. All four patients underwent attempted embolization procedures. Two patients had transarterial embolization, one with balloons and liquid adhesives, one with platinum coils and a balloon; the carotid artery was preserved in one and sacrificed in one other. In one patient, who underwent direct puncture of the carotid artery, a massive hematoma causing airway compromise required intubation and emergent surgical repair. The fistula spontaneously closed during this event. In the fourth patient, two transvenous embolizations resulted in markedly decreased flow, but diversion of residual flow to cortical veins produced a fatal pontine hemorrhage. The vascular fragility associated with Ehlers-Danlos syndrome can produce spontaneous direct carotid-cavernous fistulas and makes both diagnostic and therapeutic procedures more difficult.