Introduction: Ouster headache (CH) is a refractory headache. Low-temperature plasma radiofrequency ablation is a relatively novel technique with promising applications in neuropathic pain. It may improve the treatment of CH. Aim: To evaluate the efficacy and safety of sphenopalatine ganglion-targeted low-temperature plasma radiofrequency ablation in the treatment of patients with refractory CH. Material and methods: A retrospective cohort study including seventy-five patients with refractory duster headache who underwent computed tomography (CT)-guided sphenopalatine ganglion-targeted low-temperature plasma radiofrequency ablation between January 2015 and December 2017 at the Beijing Xuanwu Hospital was conducted. Results: Effective pain relief rate 3 months after the procedure was 96% with 40 (53.3%) patients achieving complete relief; 32 (42.7%) patients obtained partial relief and 3 (4%) patients showed no relief. The effective pain relief rate two years after the procedure remained as high as 85.3% with 29 (38.6%) achieving complete relief, 35 (46.7%) partial relief and 11 (14.7%) no relief. The procedure proved equally effective for both episodic and chronic duster headache. Complications including facial numbness, masseter weakness, facial hypoesthesia and cheek hematoma were observed, but all were mad and disappeared within 6 months. Conclusions: CT-guided low-temperature plasma radiofrequency ablation is an effective and safe strategy for refractory duster headache. For patients who have not responded to conservative treatment, this minimally invasive intervention is a reliable alternative.