Chronic cluster headache patients are often resistant to pharmacological management. Percutaneous radiofrequency ablation (RFA) of the sphenopalatine ganglion (SPG) was shown before to improve episodic cluster headache but not chronic cluster headache. We were interested to examine the effect of such intervention in patients with intractable chronic cluster headache who failed pharmacological management. Fifteen patients with chronic cluster headache, who experienced temporary pain relief following SPG block, underwent percutaneous RFA via the infrazygomatic approach under fluoroscopic guidance. Collected data include demographic variables, onset and duration of the headache, mean attack intensity (MAI), mean attack frequency (MAF), and pain disability index (PDI) before and up to 18 months after procedure. At 1-, 3-, 6-, 12-, 18-month follow-up, the MAI was 2.6, 3.2, 3.2, 3.4, 4.2, respectively (P < .0001, P < .0001, P < .0001, P < .0005, P < .003, respectively). The PDI improved from 55 (baseline) to 17.2 and 25.6 at 6 and 12 months respectively (P < .001). The MAF improved from 17 attacks/week to 5.4, 6.4, 7.8, 8.6, 8.3 at 1-, 3-, 6-, 12-, 18-month follow-up visits (P < .0001, P < .0001, P < .0001, P < .002, P < .004, respectively). Our data showed that percutaneous RFA of the SPG is an effective modality of treatment for patients with intractable chronic cluster headaches. Precise needle placement with the use of real-time fluoroscopy and electrical stimulation prior to attempting radiofrequency lesioning may reduce the incidence of adverse events.