To explore the clinical value of ultrasound combined with C-arm guiding selective semilunar ganglion radiofrequency thermocoagulation via the foramen ovale for trigeminal neuralgia.This study enrolled 48 patients diagnosed with trigeminal neuralgia between January 2021 and December 2021 in the department of pain management at Xuanwu Hospital. Patients were randomly and equally divided into the C-arm group and ultrasound combined with the C-arm group, according to a random number table. After exclusions, 42 patients were analyzed. Among them, 21 cases underwent selective semilunar ganglion radiofrequency thermocoagulation via the foramen ovale guided by the C-arm, whereas 21 cases underwent the same guided by ultrasound combined with C-arm. The number and time of punctures, the accumulative doses for radiation exposure, and puncture-related complications were recorded during the operation. Numerical rating scale scores and radiofrequency thermocoagulation-related complications were evaluated preoperatively, at 1 day, 3 days, 7 days, 1 month, and 3 months after surgery.The number and time of punctures and the accumulative doses for radiation exposure in the ultrasound-guided combined with the C-arm group were all lower than that in the C-arm-guided group (all P < 0.05). No significant difference was found in numerical rating scale scores and radiofrequency thermocoagulation -related complications between the two groups (P > 0.05). No puncture-related complications occurred in none of the groups.Ultrasound guidance combined with C-arm in puncturing semilunar ganglion via foramen ovale could be safely used with more efficiency than C-arm guidance alone and less radiation exposure.This study was registered on the Chinese Clinical Trial Registry (NO. ChiCTR2100042124; http://www.chictr.org.cn/listbycreater.aspx), and the first patient enrollment began on January 18, 2021.© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.