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Abstract Investigating the effectiveness of instructional practices provides an evidence base to inform instructional decisions. Synthesizing research studies on instructional effectiveness provides an estimate of the generalizability of effectiveness across settings, along with an exploration of factors that may moderate the impact, which cannot be achieved within individual studies. This study sought to provide a synthesis of evidence‐based instructional practices (EBIPs) particular to chemistry through meta‐analysis. Ninety‐nine studies were analyzed comprising a broader view of chemistry specific studies than past meta‐analyses. The results showed that EBIPs feature a demonstrably positive impact on students' academic performance in chemistry, although assessment topic coverage and setting size emerged as relevant moderators of impact and prevented making definitive conclusions of the relative impact of each EBIP. In examining publication bias, an asymmetric distribution of studies based on standard error(SE)and effect size was found, indicative of potential publication bias. To explore the potential impact of bias, the trim and fill method was employed resulting in a range for the overall weighted effect size from 0.29 to 0.62. The study concludes that evidence‐based instructional practices have demonstrated effectiveness even in consideration of potential publication bias, as the range of effect sizes remains positive, but highlights the continued need to publish null findings in the research literature.