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This review systematically evaluates and incorporates evidence for the use of epidural steroid injections (ESIs) in cervical and lumbar spinal stenosis and radiculopathies, assessing short-term (≤3 months) and long-term (≥6 months) improvements in pain and disability./r/nWe searched databases for randomized controlled trials (RCTs) on the efficacy of ESIs published between January 2005 and January 2021. Data analysis was performed by American Academy of Neurology methodologists. A panel of ESI experts was engaged to interpret the evidence in a clinical context. Owing to the great variability in efficacy measures used in the articles, we report differences based on any measure of success: the success rate difference (SRD)./r/nNinety RCTs met inclusion criteria. In cervical and lumbar radiculopathies, ESIs probably reduce short-term pain (SRD -24.0%, 95% CI -34.9 to -12.6, number needed to treat [NNT] 4) and disability (SRD -16.0%, 95% CI -26.6 to -5, NNT 6) and possibly decrease long-term disability (SRD -11.1%, 95% CI -25.3 to 3.6, NNT 9). There is insufficient evidence to determine whether ESIs reduce long-term pain in radiculopathies (SRD -10.3%, 95% CI -27.8 to 7.6). In lumbar spinal stenosis, ESIs possibly reduce short-term (SRD -26.2%, 95% CI -52.4 to 3.6, NNT 4) and long-term (SRD -11.8%, 95% CI -26.9 to 3.8, NNT 8) disability, but not short-term pain (SRD -3.5%, 95% CI -12.6 to 5.6). In lumbar stenosis, there is insufficient evidence to determine whether ESIs reduce long-term pain (SRD -6.5%, 95% CI -22.5 to 9.8). For cervical spinal stenosis, evidence is insufficient to determine the effectiveness of ESIs./r/nThe review affirms limited efficacy of ESIs in reducing pain and disability in cervical and lumbar radiculopathies and possibly in lumbar spinal stenosis, largely in the short term. The heterogeneity of outcome measures reported preclude presenting integrated data regarding effect size. There is controversy regarding the appropriate choice of inactive comparator treatments as a true placebo in clinical trials of ESIs. The panel recommends that future trials of ESIs use minimal meaningful clinical difference as the measure of efficacy and paraspinal muscle injection of saline as an inactive placebo.