Hepatitis C virus (HCV) infection is an important public health problem, causing significant morbidity and mortality worldwide. The prevalence of HCV infections is especially high among people who inject drugs (PWID). The efficacy of direct‐acting antiviral (DAA) therapy was evaluated herein. During 2019‐2021, a total of 321 cases who received a full course of DAA therapy and completed a 12‐week follow‐up observation were studied. The most frequent genotype (GT) was GT6 (34.9%), followed by GT1a (23.4%), GT1b (14.6%), GT2 (12.1%), and GT3 (11.8%). Increase was observed in GT6 (from 29.8% in 2019 to 44.9% in 2021) and GT3 (from 9.9% in 2019 to 16.3% in 2021) over the study years. GT2 was more likely found in patients >50 years old, while GT3 was more in younger patients (both P < .05). GT3 was also more frequently associated with moderate scores of fibrosis‐4 index (FIB‐4) (1.45 ≤ FIB‐4 ≤ 3.25, 13/38 vs 49/283; P < .05). High viral loads (>1 500 000 IU/mL) were found in 65.7% of the patients, including 21.5% showing a very high level (>6 000 000 IU/mL). Compared to other genotypes, viral loads were significantly higher in GT6 (P < .005) and lower in GT1b (P < .01). The end of treatment virologic response rate and the sustained virologic response rate at 12 weeks (SVR12) post‐treatment were both 100%. Two recurrent infections with GT6 and GT2 were noted at 16‐month and 3‐month, respectively, after achieving SVR12. The present report provides a solid evidence for the effectiveness of DAA therapy in the treatment of hepatitis C among incarcerated PWID. We believe that appropriate DAA therapy, when incorporated with active universal screening, can achieve micro‐elimination of chronic hepatitis C in incarcerated persons. Hence, the strategies should be applied to all custodial settings, especially for PWID, as an important step to eliminate hepatitis C by 2025, a goal set by the Taiwan government.