aBBreViatiONS BNI = Barrow Neurological Institute; CTN = classical trigeminal neuralgia; GKS = Gamma Knife surgery; MVD = microvascular decompression; TN = trigeminal neuralgia. OBJectiVe Gamma Knife surgery (GKS) is one of the surgical alternatives for the treatment of drug-resistant trigemi-nal neuralgia (TN). This study aims to evaluate the safety and efficacy of GKS in a large population of patients with TN with very long-term clinical follow-up. methOdS Between July 1992 and November 2010, 737 patients presenting with TN were treated using GKS. Data were collected prospectively and were further retrospectively evaluated at Timone University Hospital. The frequency and severity of pain, as well as trigeminal nerve function, were evaluated before GKS and regularly thereafter. Radiosur-gery using the Gamma Knife (model B, C, 4C, or Perfexion) was performed with the help of both MR and CT targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4–14 mm) anterior to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70–90 Gy) was prescribed. reSultS The safety and efficacy are reported for 497 patients with medically refractory classical TN who were never previously treated by GKS and had a follow-up of at least 1 year. The median age in this series was 68.3 years (range 28.1–93.2 years). The median follow-up period was 43.8 months (range 12–174.4 months). Overall, 456 patients (91.75%) were initially pain free in a median time of 10 days (range 1–180 days). Their actuarial probabilities of remaining pain free without medication at 3, 5, 7, and 10 years were 71.8%, 64.9%, 59.7%, and 45.3%, respectively. One hundred fifty-seven patients (34.4%) who were initially pain free experienced at least 1 recurrence, with a median delay of onset of 24 months (range 0.6–150.1 months). However, the actuarial rate of maintaining pain relief without further surgery was 67.8% at 10 years. The hypesthesia actuarial rate at 5 years was 20.4% and at 7 years reached 21.1%, but remained stable until 14 years with a median delay of onset of 12 months (range 1–65 months). Very bothersome facial hypesthe-sia was reported in only 3 patients (0.6%). cONcluSiONS Retrogasserian GKS proved to be safe and effective in the long term and in a very large number of patients. Even if the probability of long-lasting effects may be modest compared with microvascular decompression, the rarity of complications prompts discussion of using GKS as the pragmatic surgical first-or second-intention alternative for classical TN. However, a randomized trial, or at least a case-matched control study, would be required to compare with microvascular decompression.