Introduction: People who inject drugs (PWID) should be treated in order to eliminate hepatitis C virus (HCV) in the world. Aims: The aim of this study was to compare direct acting antivirals (DAAs) treatment of HCV for PWID and non-PWID in real life setting. Materials and methods: We performed a prospective, non-randomized, observational multi-center cohort study in 37 centers. All patients treated with DAAs therapy between April 1, 2017 to February 28, 2019 were included. In total, 2,713 patients were included in the study among which 250 were PWID and 2,463 were non-PWID. Besides patient characteristics, treatment response, follow-up and side effects of treatment were also analyzed. Results: Genotype 1a and 3 were more prevalent in PWID infected patients (20.4% vs 9.9% and 46.8% vs 5.3%). The number of naïve patients was higher in PWID (90.7% vs 60.0%), while the number of patients with cirrhosis was higher in non-PWID (14.1% vs 3.7%). The loss of follow up was higher in PWID (29.6% vs 13.6%). There was no difference in the sustained virologic response at 12 weeks after treatment (98.3% vs 98.4%), but the end of treatment response was lower in PWID (96.2% vs 99.0%). In addition, the rate of treatment completion was lower in PWID (74% vs 94.4%). Conclusion: DAAs were safe and effective in PWID. Primary measures should be taken to prevent the loss of follow-up and poor adherence in PWID patients in order to achieve World Health Organization’s objective of eliminating viral hepatitis.