OBJECTIVE Radiation therapy diminishes the risk of recurrence of incompletely removed nonfunctioning pituitary adenoma (NPA). The authors evaluated the efficacy and safety of gamma knife surgery (GKS) in patients with residual NPA following surgical debulking of the tumor. METHODS Fifty-four patients, 26 men and 28 women, ranging in age from 29 to 72 years underwent gamma knife treatment. Baseline and follow-up studies involved magnetic resonance imaging, hormone evaluation, and neuroophthalmological examination 6 and 12 months after GKS and at yearly intervals thereafter. The mean follow up after GKS was 41.1 +/- 3.1 months. Two of 52 patients undergoing follow up had a recurrence 40 and 49 months after GKS. In both of these patients the treated lesion had reduced in size, but a new lesion appeared in the contralateral side of the sella turcica. The recurrence-free interval at 5 years was 88.2% (95% confidence interval 72.6-100%). Tumor volume decreased from a baseline value of 2.3 +/- 0.2 to 1.7 +/- 0.2 cm3 at the last follow up (p < 0.001). Twenty-two patients (42.3%) had a 20% or greater reduction in tumor volume. The administered radiation dose had been significantly higher in patients who experienced tumor reduction. Visual function and motility did not deteriorate in any patient. New cases of hypogonadism, hypothyroidism, and hypoadrenalism occurred in 12.5, 8.6, and 2.3%, respectively, of assessable patients at risk. CONCLUSIONS Gamma knife surgery was effective in controlling the growth of residual NPA after previously performed maximal surgical debulking. The major advantage of GKS compared with fractionated radiotherapy seems to be a lower risk of side effects, especially a lower risk of hypopituitarism.