OBJECTIVE: To investigate the comparative effectiveness of nonsurgical interventions for adults with acute and subacute sciatica. DESIGN: Intervention systematic review with network meta-analysis. LITERATURE SEARCH: Embase, MEDLINE, Cochrane Library, and CINAHL were searched up to June 7, 2024. STUDY SELECTION CRITERIA: Randomized controlled trials of nonsurgical interventions in adults (aged 18 years or older) with acute or subacute sciatica (less than 3 months) were included. DATA SYNTHESIS: The primary outcomes were leg pain intensity and physical function at different follow-up time points. Secondary outcomes were adverse events, mental health, and low back pain intensity. Two reviewers independently conducted screening, data extraction, and risk-of-bias assessment. Random-effects network meta-analysis was conducted, and confidence was evaluated by the Confidence in Network Meta-Analysis (CINeMA) method. RESULTS: Forty randomized controlled trials (5381 participants) were included. At short-term follow-up, compared to sham treatment/placebo, the most efficacious interventions for leg pain intensity were NSAIDs plus physical therapy modalities, antibiotics, and antidepressants. Music therapy was effective for improving physical function at short-term follow-up. At long-term follow-up, steroids had a significant effect in reducing leg pain and improving physical function. No intervention showed a significant increase in adverse events compared with sham-treatment/placebo. All the evidence was based on very low confidence, primarily due to within-study bias and imprecision in effect estimates. CONCLUSIONS: Very low-confidence evidence supported some nonsurgical interventions for improving leg pain intensity and physical function in people with acute and subacute sciatica.

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