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Objective To investigate the clinical efficacy of X-ray imaging combined with skin stimulation potential-guided percutaneous radiofrequency thermocoagulation of the Gasserian ganglion for treatment of primary trigeminal neuralgia. Design This is a prospective, randomized study. Sixty patients with primary trigeminal neuralgia were randomly assigned to a study group or control group. In the study group, the patients underwent X-ray imaging combined with skin stimulation potential-guided percutaneous radiofrequency thermocoagulation of the Gasserian ganglion. The patients in the control group underwent C-arm X-ray-guided puncture through the foramen ovale, and then the puncture needle was microscopically adjusted according to the intensity of the masticatory muscle response and the patients' reactions. Puncture success, postoperative adverse reactions, and short- and middle-term analgesic efficacies were statistically compared between the two surgical approaches. Results The incidence of postoperative side effects was significantly reduced, and immediate and mid-term analgesic efficacy was better in patients in the study group comparing with those in the control group ( P < 0.01). Conclusion Using skin stimulation potential-guided puncture may enable more accurate microscopic adjustment of the targets localization damaged by radiofrequency and significantly enhanced clinical efficacy in this study. [ABSTRACT FROM AUTHOR]