Background Opioid agonist therapy (OAT) uptake has been associated with multiple positive health outcomes among people who inject drugs (PWID). This study evaluated the pattern of OAT uptake among PWID in two consecutive national bio-behavioral surveillance surveys (2010 and 2014) in Iran.Methods Data were obtained from two national bio-behavioral surveillance surveys (N2010 = 1,783 and N2014 = 2,166) implemented using convenience sampling at the harm reduction facilities and street venues in 10 geographically diverse urban centers across Iran. Multivariable logistic regression models were built to determine the correlates of OAT uptake for the 2014 survey and adjusted odds ratios (AORs) and 95% confidence intervals (CI) were reported.Results The prevalence of OAT uptake decreased from 49.2% in 2010 to 45.8% in 2014 (P-value = 0.033). OAT uptake varied across the studied cities ranging from 0.0%-69.3% in the 2010 survey and 3.2%-75.5% in the 2014 survey. Ever being married (AOR = 1.40; 95% CI: 1.12, 1.75), having a history of incarceration (AOR = 1.56; 95% CI: 1.16, 2.09), and human immunodeficiency virus (HIV) sero-positivity (AOR = 1.63; 95% CI: 1.08, 2.5) were associated with OAT uptake. Conversely, PWID who reported using only non-opioid drugs (AOR = 0.43; 95% CI: 0.26, 0.71) and those who reported concurrent use of opioid and non-opioid drugs (AOR = 0.66; 95% CI: 0. 0.51, 0.86) were less likely to uptake OAT. Conclusions Although OAT uptake among PWID in Iran is above the 40% threshold defined by the World Health Organization, there remains significant disparities across urban settings in Iran. Importantly, the OAT services appear to be serving high-risk PWID including those living with HIV and those with a history of incarceration. Evaluating service integration including mental health, HIV and hepatitis C virus care, and other harm reduction services may support the optimization of health outcomes of OAT across Iran.