Science depends on trustworthy evidence. Thus, a biased scientific record is of questionable value because it impedes scientific progress, and the public receives advice on the basis of unreliable evidence that has the potential to have far-reaching detrimental consequences. Meta-analysis is a technique that can be used to summarize research evidence. However, meta-analytic effect size estimates may themselves be biased, threatening the validity and usefulness of meta-analyses to promote scientific progress. Here, we offer a large-scale simulation study to elucidate how p-hacking and publication bias distort meta-analytic effect size estimates under a broad array of circumstances that reflect the reality that exists across a variety of research areas. The results revealed that, first, very high levels of publication bias can severely distort the cumulative evidence. Second, p-hacking and publication bias interact: At relatively high and low levels of publication bias, p-hacking does comparatively little harm, but at medium levels of publication bias, p-hacking can considerably contribute to bias, especially when the true effects are very small or are approaching zero. Third, p-hacking can severely increase the rate of false positives. A key implication is that, in addition to preventing p-hacking, policies in research institutions, funding agencies, and scientific journals need to make the prevention of publication bias a top priority to ensure a trustworthy base of evidence. (PsycInfo Database Record (c) 2020 APA, all rights reserved).