Ultrasound (US)-guided injections for chronic pain has multiple advantages over traditional radiologic method. The study was performed to exam the clinical outcomes of lumbar transforaminal epidural injection (LTFEI) between US and fluoroscopy (FL) guidance for lumbar radiculopathy (LRP).A total of 164 patients with LRP were randomly assigned into US and FL group to receive LTFEI in a 1:1 ratio. Pain relief and functional disability were assessed by numeric rating scale (NRS) and Modified Oswestry Disability Questionnaire (MODQ) scores before treatment, 1 month and 3 months post-intervention. Contrast spread pattern, fluoroscopic image number and complications were also recorded. The primary outcome was accurate rate of contrast dispersing into lumbar epidural space, and non-inferiority margin was predefined at -15 %.The accuracy of LTFEI was 90.2 % and 91.5 % in US and FL group, and the lower limit of the 95 %CI of mean difference between two modalities (-4.9 % (95 %CI: -12.8 %, 3.1 %)) was above the non-inferiority margin. Procedure time in US group (531.90 ± 67.12 s) was shorter than FL group (904.20 ± 120.20 s) (p < 0.05), while radiation dosage in the US group was lower than in the FL group (3047.20 ± 569.53 vs. 8807.50 ± 1039.10 μGy m2, p < 0.001). Both groups didn't differ in pain reduction (F = 1.050, p = 0.306) and functional improvement (F = 0.103, p = 0.749) during follow-up period. No severe complications occurred in both groups.US-guided LTFEI confirmed by FL was not inferior to conventional FL method in terms of accurate rate of lumbar epidural contrast dispersion. Effective pain relief and functional ability improvement were comparable between two modalities, and US technique had advantages of less radiation exposure and possible facilitation of avoiding critical vessels around intervertebral foramen.Copyright © 2023. Published by Elsevier B.V.