BackgroundPeople who use drugs (PWUD) are considered as one of the main at-risk populations for Hepatitis B virus (HBV) infection. We conducted a systematic review on the prevalence of HBV infection among PWUD in Iran.MethodsConsistent with PRISMA guideline, international (Medline, Web of Science, Scopus, and Embase) and national (Scientific Information Database) databases were searched using a comprehensive search strategy up to September 2019. The retrieved records were reviewed, and experts were contacted for unpublished studies. Studies on Iranian PWUD reporting HBV surface Antigen (HBsAg) prevalence among people who inject drugs (PWID) and non-injecting PWUD were included. HBsAg prevalence was pooled for PWID and non-injecting PWUD and for other subgroups using random-effects model meta-analysis. The trend of HBV prevalence over time was investigated using meta-regression analysis.ResultsOverall, 35 studies reported data on HBV infection among PWID (33 studies) and non-injecting PWUD (11 studies). The pooled prevalence of HBsAg among PWID was 4.8% (95% CI 3.7–6.2). The only risk factor significantly associated with the odds of positive HBsAg in PWID was the previous history of imprisonment (OR 1.72, 95% CI 1.29–2.30, p value = 0.000). The pooled estimate of HBsAg among non-injecting PWUD was 2.9% (95% CI 2.5–3.2). Time trend analyses showed significant decrease in HBV prevalence among PWID reaching from 8.2% (95% CI 3.9–16.5) in 2004–2006 to 3.1% (95% CI 2.3–4.1) in 2016 and later (b = -0.07; p value = 0.05). No significant trend was detected for non-injecting PWUD.ConclusionThe prevalence of HBV infection among non-injecting PWUD and even PWID was not considerably higher than the Iranian general population. This might be the result of extensive harm reduction interventions in Iran. However, it seems that there are subgroups of PWID, who do not adequately benefit from existing harm reduction interventions. Future programs should more specifically target these high-risk groups.