Percutaneous glycerol injection into Meckel's cavity is widely used to treat trigeminal neuralgia. Reports published to date summarized clinical experiences in small or intermediately sized groups of patients. The efficacy of this procedure in a large group of patients has not been evaluated so far. From December 1983 to November 2008, patients with primary trigeminal neuralgia were treated in our clinic using percutaneous glycerol injection into Meckel's cavity which was conducted according to the Hakanson's anterior puncture method with some modifications. In total, 4012 patients (2205 female) with a mean age of 56.5 (23-87) years were treated. The majority of patients (99.23%) experienced unilateral pain, while a small cohort of patients (31; 0.77%) had bilateral pain. The immediate success rate of the procedure was 97.1%. There was a significant (P < 0.01) positive correlation between the presence of cerebrospinal fluid (CSF) outflow and the curative effect. Follow-up was done in 3157 patients for the period of 1-25 years. The long-term success rate was 81.18%. No serious adverse effects were observed. The procedure is very effective and applicable to a wide variety of patients with trigeminal neuralgia. The presence of CSF outflow during puncture predicts better immediate and long-term outcomes.