BACKGROUND Most reports on basilar artery (BA) occlusive disease have retrospectively described single cases or small patient series. OBJECTIVE To assess clinical and vascular features, stroke mechanisms, etiologies, and outcome of moderate to severe BA occlusive disease among 407 patients in the New England Medical Center Posterior Circulation Registry, the largest prospective series of consecutively collected patients with posterior circulation ischemia to date. RESULTS We studied 87 patients and identified 3 patient groups with distinct vascular, clinical, etiological, and prognostic characteristics: isolated BA disease (39 patients [44.8%]), BA involvement as part of widespread posterior circulation atherosclerosis (36 patients [41.4%]), and embolism to the BA (12 patients [13.8%]). Vascular risk factors were common and often multiple. Most patients (54 [62.1%]) had involvement of the midportion of the BA. Fifty-eight patients (66%) initially had transient ischemic attacks, of whom 34 (58.6%) progressed to stroke. Transient ischemic attacks were usually multiple, lasted for several months, and increased in frequency as the stroke approached. When an infarct was present, the middle posterior intracranial territory was most often involved (66 patients [75.9%]). Outcome was much better than previously assumed. The mortality rate was 2.3%, and 62 patients (almost 75%) had minor or no deficits at follow-up. Outcome was best among patients with widespread atherosclerotic disease and worst in 7; (58.3%, with major disability) of 12 patients with embolism to the BA. Distal territory involvement, embolism, BA occlusion, decreased level of consciousness, tetraparesis, and abnormal pupils were significant predictors of poor outcome. CONCLUSIONS Inclusion of patients into 1 of the BA groups and early identification of predictive outcome factors guide diagnostic evaluation and treatment.