Background: Limited empirical evidence exists for hepatitis C virus (HCV) treatment-asprevention. The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study assessed HCV treatment-as-prevention in four Australian prisons.Methods: SToP-C is a non-randomised trial, including a pre/post analysis within a prospective longitudinal cohort of people incarcerated in two maximum-(male) and two medium-security prisons (one male, one female). All prison inmates at least 18 years were eligible for enrolment.Participants were enrolled from late-2014 to 2019. Following HCV testing, participants were monitored for risk behaviors and HCV, among three sub-populations: 1) uninfected (HCV antibody negative); 2) previously infected (HCV antibody positive, HCV RNA negative); 3) infected (HCV antibody and HCV RNA positive). Uninfected and previously infected (at-risk) participants were followed every 3-6 months for HCV primary infection and re-infection, respectively. Infected participants were assessed for treatment, initially standard of care treatment (by prison health services), followed by direct-acting antiviral (DAA) treatment scale-up from mid-2017 (12 weeks sofosbuvir/velpatasvir, through SToP-C). Participants were followed until study closure in November 2019. The primary study outcome was HCV incidence compared between pre-and post-treatment scale-up periods among participants at risk of HCV primary infection or re-infection. The trial was registered with ClinicalTrials.gov (identifier: NCT02064049) Findings: Of 3,691 participants enrolled, 719 (19%) had detectable HCV RNA and 2,965 were at-risk of primary infection (n=2,240) or re-infection (n=725) at baseline. DAA treatment was initiated in 349/499 eligible participants during the treatment scale-up period. Among at-risk population with longitudinal follow-up (n=1,643; median age 33 years; 82% male), 31% reported injecting drug use in prison. HCV incidence declined by 48%, from 8.31 to 4.35/100 person-years between pre-and post-treatment scale-up periods [Incidence Rate Ratio (IRR): 4 0.52, 95%CI: 0.36, 0.78]. Incidence of primary infection declined from 6.64 to 2.85/100 personyears (IRR: 0.43, 95%CI: 0.25, 0.74), while incidence of re-infection declined from 12.36 to 7.27/100 person-years (IRR: 0.59, 95%CI: 0.35, 1.00). Among participants reporting injecting drug use in the current imprisonment, incidence of primary infection declined from 39.08 to 14.03/100 person-years (IRR: 0.36, 95%CI: 0.16, 0.80), and incidence of re-infection declined from 15.26 to 9.34/100 person-years (IRR: 0.61, 95%CI: 0.34, 1.09). Adjusted analysis indicated a significant reduction in HCV risk between pre-and post-treatment scale-up periods (adjusted Hazard Ratio: 0.50, 95% CI: 0.33, 0.76).Interpretation: DAA treatment scale-up was associated with reduced HCV incidence in prison, indicative of HCV treatment-as-prevention. The findings support broad DAA treatment scale-up among incarcerated populations.