The role of radiosurgery in the treatment of cavernous malformations (CMs) remains controversial. It is frequently recommended only for inoperable lesions that have bled at least twice. Rehemorrhage can carry a substantial risk of morbidity, however. The authors reviewed their practice of treating deep-seated inoperable CMs to assess the complication rate of radiosurgery, the impact that radiosurgery might have on rebleeding, and whether a more active, earlier intervention is justified in managing this condition. The authors performed a retrospective analysis of 113 patients with 79 brainstem and 39 thalamic/basal ganglia CMs treated with Gamma Knife surgery. Lesions were stratified into 2 groups: those that might be lower risk with no more than 1 symptomatic bleed before radiosurgical treatment and those deemed high risk with multiple symptomatic hemorrhages before treatment. Forty-one CMs had multiple symptomatic hemorrhages before radiosurgery with a first-ever bleed rate of 2.9% per lesion per year, a rebleed rate of 30.5% per lesion per year, and a median time of 1.5 years between the first and second bleeds. In this group the rebleed rate decreased to 15% for the first 2 years after radiosurgery and declined further to 2.4% thereafter. Pretreatment multiple bleeds led to persistent deficits in 72% of the patients. Seventy-seven CMs had no more than 1 symptomatic bleed before radiosurgery, making for a lifetime bleed rate of 2.2% per lesion per year. The short period between the presenting bleed and treatment (median 1 year) makes the natural history in this group uncertain. The rate of hemorrhage in the first 2 years after treatment was 5.1%, and 1.3% thereafter. Pretreatment hemorrhages resulted in permanent deficits in 43% of the patients in this group, a rate significantly lower than in the multiple-bleeds group (p < 0.001). Posttreatment hemorrhages led to persistent deficits in only 7.3% of the patients. Permanent adverse radiation effects were rare (7.3%) and minor in both groups. Stereotactic radiosurgery is a safe management strategy for CMs in eloquent sites with the marked advantage of reducing rebleed risks in patients with repeated pretreatment hemorrhages. The benefit in treating CMs with a single bleed is less clear. Note, however, that repeated hemorrhage carries a significant risk of increased morbidity far in excess of any radiosurgery-related morbidity, and the authors assert that this finding justifies the early active management of deep-seated CMs.