Background: Although gamma knife radiosurgery (GKRS) has been shown to be safe and effective for the treatment of trigeminal neuralgia (TN), there are few studies that report the results of a second GKRS. Method: Between May 22, 1998 and April 1, 2003, we treated 335 primary TN patients with GKRS. All received a maximum dose of 75 Gy to the cisternal trigeminal nerve. 45 patients with recurrent or persistent TN were treated with a maximum dose of 40 Gy at a second GKRS and were available for at least 6 months of follow-up. Results: Final pain relief (mean of 15 months after second GKRS) was 50% or greater in 28 of the 45 patients (62.2%). Patients who had no neurosurgical procedure prior to their first GKRS were more likely to have pain relief of 50% or greater following the second GKRS (p = 0.042). Significant new dysesthesias (score greater than 5 on a scale of 0–10) developed in 2 patients (4.4%). Conclusion: Repeat GKRS has a good chance of relieving TN pain without complications and is more likely to relieve pain in those who did not have any procedure prior to their first GKRS.