Injection drug use is the primary driver of the human immunodeficiency virus HIV epidemic in Iran. We characterized people who inject drugs (PWID) living in Iran who had never received opioid agonist therapy (OAT) and examined barriers to OAT uptake. We recruited 2,684 PWID with a history of drug injection in the previous 12 months using a respondent-driven sampling approach from 11 geographically dispersed cities in Iran. The primary outcome was no lifetime uptake history of OAT medications. The lifetime prevalence of no history of OAT uptake among PWID was 31.3%, with significant heterogeneities across different cities. In the multivariable analysis, younger age, high school education or above, no prior incarceration history, and shorter length of injecting career was significantly and positively associated with no history of OAT uptake. Individual-level barriers, financial barriers, and system-level barriers were the main barriers to receiving OAT. PWID continue to face preventable barriers to accessing OAT, which calls for revisiting the OAT provision in Iran.