Background: Hepatitis C virus (HCV) infection is one of the major public health challenges generating a relevant burden. High-risk groups, including people who inject drugs (PWID), are at serious risk for developing HCV. In recent years, several investigations have been conducted in Iran to assess the prevalence e of HCV among PWID. The aim of the present study was to synthesize the literature performing a comprehensive search and meta-analysis. Methods: A comprehensive literature search was carried out from January 2000 to September 2019. Several international databases, namely Scopus, PubMed/MEDLINE, Embase, ISI/Web of Science, PsycINFO, CINAHL, the Cochrane Library and the Directory of Open Access Journals (DOAJ), as well as Iranian databases (Barakathns, SID and MagIran), were consulted. Eligible studies were identified according to the following PECOS (population, exposure, comparison/comparator, outcome and study type) criteria: i) population: Iranian population; ii) exposure: injection drug users; iii) comparison/comparator: type of substance injected and level of substance use, iv) outcome: HCV prevalence; and v) study type: cross-sectional study. After finding potentially related studies, authors extracted relevant data and information based on an ad hoc Excel spreadsheet. Extracted data included the surname of the first author, the study journal, the year of publication, the number of participants examined, the type of diagnostic test performed, the number of positive HCV patients, the number of participants stratified by gender, the reported prevalence, the duration of drug injection practice and the history of using a shared syringe. Results: Forty-two studies were included. 15,072 PWID were assessed for determining the prevalence of HCV. The overall prevalence of HCV among PWID in Iran was computed to be 47% (CI 95: 39-56). The prevalence ranged between 7 and 96%. Men and subjects using a common/shared syringe were 1.46 and 3.95 times more likely to be at risk, respectively. Conclusion: The findings of the present study showed that the prevalence of HCV among PWIDs in Iran is high. The support and implementation of ad hoc health-related policies and programs that reduce this should be put into action.