Abstract: Objective To compare the effectiveness and safety of ultrasound-guided versus X-ray-guided radiofrequency neurotomy on posterior medial branch for treatment of lumbar facet joint-related back pain. Methods A total of 90 patients with lumbar facet joint-related back pain treated in the Shanghai Changhai Hospital from January 2016 to January 2018 were enrolled into this study. The patients were randomly assigned into two groups, with 45 patients in each group. Patients in ultrasound-guided group were treated with radiofrequency neurotomy on posterior medial branch under the guidance of ultrasound, while patients in X-ray group were treated under the guidance of X-ray. The visual analog scale (VAS) was used to evaluate pain and curative effect before and after treatment. We rated efficacy as effective when post-treatment VAS score decreased by 50% or more.The Oswestry disability index (ODI) was used to evaluate the function before and after treatment. Results There was no significant difference in VAS scores between the two groups before treatment. The VAS scores and ODI index significantly reduced in both groups at 1 week, 3 months, 6 months, and 12 months after treatment compared to pre-treatment, while no significant difference was found between these two groups. At 3 months after treatment, 86.7% patients in the ultrasound-guided group and 82.2% patients in the X-ray-guided group achieved good outcome (P>0.05). At 12 months after treatment, both the two treatments were still effective in more than 50% patients. As compared to X-ray-guided group, the operating time in the ultrasound-guided group was much shorter (22.2±3.5 min vs 32.4±6.9 min, P<0.01). No complication was found in both groups. Conclusion The ultrasound-guided radiofrequency neurotomy on posterior medial branch is effective and safe for treatment of lumbar facet joint-related back pain, and its efficacy is equal to the X-ray-guided radiofrequency, which is worthy of clinical application.