Sixty patients with trigeminal neuralgia who did not have a response to pharmacologic treatment (including 22 who had no response to conventional surgical treatment) underwent stereotactic radiosurgical treatment with the Leksell Gamma Knife. A radiosurgical maximum dose of 70 Gy was delivered to the trigeminal nerve root adjacent to the pons via a 4-mm collimator helmet in 51 patients who presented with trigeminal neuralgia unrelated to tumors. In these patients, the root was localized by stereotactic MRI. Follow-up assessment of pain relief was accomplished by a third party not involved in the patients' clinical care. Within a latency period of 1 day to 4 months following the treatment, 38 of 51 patients (74.5%) were completely free of pain and eventually all medications were tapered off. An additional seven patients (13.7%) experienced reductions in pain from 50 to 90% and utilized little or no medications. Patients who had no prior surgical intervention fared much better than those who had previous surgery to relieve their facial pains. At last follow-up, a mean of 16.3 months (range 6-36 months) after treatment, 41 patients (80.4%) remained pain-free or had marked pain reduction. There were four patients with recurrent pain. All 26 patients with classical symptoms of trigeminal neuralgia with no atypical features who had no prior surgery, had complete or nearly complete pain relief, and none of these patients had recurrent pain. Nine patients with trigeminal neuralgia due to tumors received standard radiosurgical treatment directed at their tumors, and eight of nine (88.8%) had pain relief. Of the total of 60 patients treated for trigeminal neuralgia, 49 (81.7%) experienced complete or nearly complete relief of pain at last follow-up. Only one patient with pre-existing facial sensory loss due to a tumor had a mild increase in facial numbness. No other patient experienced either loss of facial sensation or any other complication. Gamma Knife radiosurgery appears to be a minimally invasive, safe, and effective therapy of trigeminal neuralgia.