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Impacts of rational number interventions among U.S. students in Grades 3 through 9 with mathematics difficulties are examined using a systematic review and meta-analysis. The primary goal of the meta-analysis was to identify instructional practices that are key drivers of student impacts. From approximately 1,200 published and unpublished study records, we identified 28 studies that met our inclusion criteria and coded the interventions for their instructional practices, intervention characteristics, and study design features. The random-effects mean effect size across all 28 studies (90 effect sizes) was 0.68 ( SE = 0.08, p < .001, 95% confidence interval [CI]: [0.51, 0.85]). The 95% prediction interval was −0.36 to 1.8. Using meta-regression techniques, we found the teaching of mathematical language ( β = 0.50) and the use of the number line ( β = 0.47) during intervention to be significantly associated with positive impacts when adjusted for controls. We discuss implications for intervention practice and study limitations along with the challenges of examining complex, multifaceted interventions.