Intracranial aneurysms are an unusual complication of sickle-cell anemia; only 15 patients have been described in the world literature. An additional 15 patients with sickle-cell anemia and subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms are presented. There was a high incidence of multiple aneurysms (60%); some of which were in unusual locations. The clinical and pathological features of this series of patients have provided a paradigm for acquired aneurysm formation that may be applicable to other intracranial aneurysms. Thirteen patients underwent craniotomy and clip ligation; the perioperative management of these patients is discussed. Of these 13, eight had a good recovery, three were left with moderate disability, one patient died of surgical complications, and one died of complications related to sickle-cell anemia. Two of the 15 patients died of SAH. The authors propose that endothelial injury from the abnormal adherence of sickle erythrocytes to the endothelium is the initiating event in arterial wall injury. Subsequently, there is fragmentation of the internal elastic lamina and degeneration of the smooth-muscle layer. Hemodynamic stress at these loci of arterial wall damage results in aneurysm formation. This hypothesis also explains other cerebrovascular manifestations of sickle-cell anemia, namely vaso-occlusive disease and hemorrhage without aneurysm formation. Pathological material from this series and data from the literature are presented to support this hypothesis.