This study was conducted to evaluate the efficacy, based on 12- to 70-month follow-up data, of radiofrequency (RF) lesions of the sphenopalatine ganglion made in patients suffering from cluster headache. Sixty-six patients suffering from either episodic (Group A, 56 patients) or chronic (Group B, 10 patients) cluster headache who were not responsive to pharmacological management were treated by RF lesioning in the sphenopalatine ganglion. Complete relief of pain was achieved in 34 (60.7%) of 56 patients in Group A and in three (30%) of 10 patients in Group B. No relief was found in eight patients (14.3%) in Group A and in four (40%) in Group B. The mean time of follow up was 29.1 +/- 10.6 months in Group A and 24 +/- 9.7 months in Group B, ranging from 12 to 70 months. With regard to side effects and complications, temporary postoperative epistaxis was observed in eight patients and a cheek hematoma in 11 patients; a partial RF lesion of the maxillary nerve was inadvertently made in four patients. Nine patients complained of hypesthesia of the palate, which disappeared in all cases within 3 months. The authors conclude that RF lesioning in the sphenopalatine ganglion via the infrazygomatic approach may be performed in patients suffering from cluster headache that does not respond to pharmacological therapy.