OBJECTIVE: To evaluate the efficacy of high-velocity low-amplitude thrust (HVLAT) manipulations in patients with cervical, thoracic, and lumbar radiculopathy. DESIGN: Intervention systematic review. LITERATURE SEARCH: Five electronic databases were searched from inception to May 2024. STUDY SELECTION CRITERIA: Randomized controlled trials comparing HVLAT to different interventions in patients with cervical, thoracic, or lumbar radiculopathy were eligible, if they reported outcomes related to pain intensity, disability, range of motion, and/or health-related quality of life. DATA SYNTHESIS: Data were pooled using a random-effects model. Heterogeneity was assessed using the I2 statistic. The risk of bias (RoB) was assessed with the revised Cochrane RoB tool (RoB 2). The certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: Eleven trials (N = 991) were included. HVLAT was associated with significant pain reduction compared to sham HVLAT (mean difference (MD) -1.20; 95% confidence interval (CI) -1.90 to -0.50) and to nonrecommended interventions (MD -1.16; 95% CI -1.54 to -0.77) in both cervical and lumbar radiculopathy. HVLAT was associated with reduced pain compared to conventional physical therapy alone (MD -1.26; 95% CI -2.20 to -0.32) at short- and medium-term follow-up. There were no differences at long-term follow-up. The overall RoB was high; the certainty of evidence ranged from very low to moderate. CONCLUSION: HVLAT could reduce pain and disability in patients with cervical and lumbar radiculopathy in the short term and medium term compared with sham HVLAT interventions, conventional physical therapy alone, and spinal mobilization, but not if compared to spinal mobilization with leg movement.

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