The aims of this study were to assess the incidence of, and risk factors for, delayed toxicity following gamma knife stereotactic radiosurgery (GKRS) to lesions in and adjacent to the brainstem. We retrospectively evaluated the delayed toxicity of GKRS following the treatment of 114 lesions in and adjacent to the brainstem in 107 patients. The median tumor volume was 6.2 cm(3) and the median dose to the tumor margin was 16Gy. The mean follow-up was 40 months. Thirteen patients (12%) demonstrated clinical evidence of delayed toxicity, with a median latency to the development of toxicity of 6 months. The actuarial incidence of toxicity at 1 year and 5 years was 10.2% and 13.8%. Larger tumor volume (p=0.02) and larger treatment volume (p=0.04) were associated with an increased incidence of delayed toxicity. Large lesions adjacent to the brainstem have a higher than previously suspected rate of delayed toxicity.