Stereotactic radiosurgery has been shown to afford a reasonable chance of local tumor control. However, new brain metastasis can arise following successful local tumor control from radiosurgery. This study evaluates the timing, number, and risk factors for development of subsequent new brain metastasis in a group of patients treated with stereotactic radiosurgery alone. One hundred seventeen patients with histologically confirmed metastatic cancer underwent Gamma Knife surgery (GKS) to treat all brain metastases demonstrable on MR imaging. Patients were followed clinically and radiologically at approximately 3-month intervals for a median of 14.4 months (range 0.37-51.8 months). Follow-up MR images were evaluated for evidence of new brain metastasis formation. Statistical analyses were performed to determine the timing, number, and risk factors for development of new brain metastases. The median time to development of a new brain metastasis was 8.8 months. Patients with 3 or more metastases at the time of initial radiosurgery or those with cancer histologies other than non-small cell lung carcinoma were found to be at increased risk for early formation of new brain metastasis (p < 0.05). The mean number of new metastases per patient was 1.6 (range 0-11). Those with a higher Karnofsky Performance Scale score at the time of initial GKS were significantly more likely to develop a greater number of brain metastases by the last follow-up evaluation. The timing and number of new brain metastases developing in patients treated with GKS alone is not inconsequential. Those with 3 or more metastases at the time of radiosurgery and those with cancer histology other than non-small cell lung carcinoma were at greater risk of early formation of new brain metastasis. Frequent follow-up evaluations, such as at 3-month intervals, appears appropriate in this patient population, particularly in high-risk patients. When detected early, salvage treatments including repeat radiosurgery can be used to treat new brain metastasis.