Background: Cluster headache is a variant of primary neurovascular headaches. some patients with cluster headache are not responsive to medical treatment and may benefit from interventional modalities, including sphenopalatine ganglion block and denervation. Objectives: Our purpose was to evaluate the efficacy of sphenopalatine ganglion block/denervation in the treatment of cluster headache. Methods: In this study, we performed the sphenopalatine ganglion block for patients with cluster headaches, intractable to medical therapy, who were referred to our pain clinic between 2014 and 2018. We registered the following information for all patients: demographic data, pain relief, and pain intensity. First, we conducted a prognostic C-arm-guided sphenopalatine ganglion block. If there was at least 50% pain relief within the first 5 h, then we denervated the ganglion by radiofrequency ablation. The main outcome of the study (dependent variable) was pain relief. We followed the patients for 6 months. Results: Among 23 enrolled patients, 19 consented to interventional treatment. Fifteen out of 19 patients (79%) had an acceptable response to the prognostic block. Ultimately, 11 patients underwent ganglion denervation, and 4 patients did not consent for ganglion ablation. Pain relief at intervals of 48 h, and 1, 3, and 6 months after ganglion denervation was 77, 59, 50, and 31 percent, respectively. Conclusions: Sphenopalatine ganglion conventional radiofrequency denervation can effectively decrease the pain intensity of the patients with cluster headache for at least several months.