Summary Direct-acting antivirals (DAAs) represent an opportunity to improve hepatitis C virus (HCV) care cascade. This combined with improved harm reduction interventions may lead to HCV elimination especially in people who inject drugs (PWID). We assessed the effectiveness/cost-effectiveness of improvements in harm reduction and chronic hepatitis C (CHC) care cascade in PWID in France. We used a dynamic model of HCV transmission and CHC natural history and evaluated the following: improved needle/syringe programmes-opioid substitution therapies, faster diagnosis/linkage to care, earlier treatment initiation, alone and in combination among active PWID (mean age = 36). Outcomes were as follows: life expectancy in discounted quality-adjusted life years (QALYs); direct lifetime discounted costs; incremental cost-effectiveness ratio (ICER); number of infections/reinfections. Under the current practice, life expectancy was 15.846 QALYs, for a mean lifetime cost of ?20 762. Treatment initiation at F0 fibrosis stage alone was less effective and more costly than faster diagnosis/linkage to care combined with treatment initiation at F0, which increased life expectancy to 16.694 QALYs, decreased new infections by 37%, with a ICER = ?5300/QALY. Combining these interventions with harm reduction improvements was the most effective scenario (life expectancy = 16.701 QALYs, 41% decrease in new infections) but was not cost-effective (ICER = ?105 600/QALY); it became cost-effective with higher initial HCV incidence rates and lower harm reduction coverage than in our base-case scenario. This study illustrated the high effectiveness, and cost-effectiveness, of a faster diagnosis/linkage to care together with treatment from F0 with DAAs. This ?Test and treat? strategy should play a central role both in improving the life expectancies of HCV-infected patients, and in reducing HCV transmission.