BACKGROUND: People who inject drugs (PWID) continue to experience the highest burden of hepatitis C virus (HCV). We aimed to characterize HCV antibody prevalence, determinants of infection, and the cascade of engagement in HCV care among PWID in Iran. METHODS: Participants were recruited in 11 cities of Iran using respondent-driven sampling. PWID underwent a structured interview capturing measures on socio-demographics, behaviors, and the HCV cascade of care. HCV and HIV were tested using antibody rapid tests. Multivariable logistic regression models identified characteristics associated with HCV seropositivity. RESULTS: HCV antibody prevalence was 26.0% among 2684 PWID enrolled. Of 699 participants who were HCV antibody positive, 88 (12.6%) were aware of past infections. HCV antibody prevalence was associated with older age (adjusted odds ratio [aOR] 2.09; 95% CI 1.18, 3.71), lower education (aOR 1.31; 95% CI 1.02, 1.69), >10 years of injecting (aOR 6.03; 95% CI 4.10, 8.85), methamphetamine injection (aOR 1.46; 95% CI 1.07, 1.99), daily injection drug use (aOR 1.26; 95% CI 1.01, 1.58), needle/syringe sharing (aOR 2.04; 95% CI 1.24, 3.34), recent incarceration (aOR 1.74; 95% CI 1.30, 2.32), and HIV seropositivity (aOR 7.93; 95% CI 4.12, 15.24). Additionally, 12.0% had ever tested for HCV, 4.0% had previously tested reactive for HCV antibody, and 3.7% had received an HCV diagnosis. Of diagnosed cases, 44.4% were linked to care, 15.2% initiated treatment, and 3.0% achieved sustained virologic response. CONCLUSION: Our data show a high prevalence of HCV antibody and low engagement in HCV care, underscoring an unmet need for HCV prevention, screening, and treatment among PWID in Iran. HCV prevention and treatment programs tailored for PWID are needed to enhance harm reduction efforts and access to HCV care in Iran.