SummaryThis systematic review, meta‐analysis and meta‐regression assessed the prevalence of restless legs syndrome (RLS) in the general adult population. Studies identified in Scopus, PubMed, Web of Science, and PsycInfo between January 2000 and February 2022 were included if they used a case–control or cross‐sectional design and reported data regarding the prevalence of RLS. The protocol was pre‐registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022300709). A total of 97 studies including 483,079 participants from 33 different countries met the eligibility criteria. The Newcastle Ottawa Scale was used to evaluate the methodological quality, and the fill‐and‐trim method was used to correct probable publication bias, while the jack‐knife method was performed to assess small study effect. The corrected overall pooled prevalence of RLS was 3% (95% confidence interval [CI] 1.4%–3.8%). The pooled prevalence of RLS syndrome was affected by methodological quality (no data from non‐respondents in the included studies), gender (higher among women), study design (lower prevalence in case–control versus cohort and cross‐sectional studies). The figures for corrected pooled prevalence among men, women, alcohol consumers and smokers were 2.8% (95% CI 2%–3.7%); 4.7% (95% CI 3.2%–6.3%); 1.4% (95% CI 0%–4.2%); and 2.7% (95% CI 0%–5.3%), respectively. The prevalence among male and female participants was lower in community‐based versus non‐community‐based studies. Moreover, the prevalence was higher in developed versus developing countries and among elders versus adults. In conclusion, RLS is a common disorder in the general adult population, with a higher prevalence in women; however, prevalence data are affected by study design and quality.