Introduction - The objective of this study was to compare mortality, the incidence of hepatocellular carcinoma (HCC), and decompensated cirrhosis (DC) in patients treated versus untreated with direct-acting antivirals (DAAs) in the French prospective Hepather cohort. Patients and Methods - Adults with chronic HCV infection, without hepatitis B coinfection or a history of DC, HCC, liver transplantation, or treatment with first-generation protease inhibitors, were enrolled between August 2012 and December 2015. The association between DAA treatment and the occurrence of events was analyzed using time-dependent proportional hazards Cox models. Results - 9,895 patients were included: 7,344 treated and 2,551 untreated (median follow-up of 33 months [IQR: 24–41]). Death, HCC, and DC were observed in 218 (129 treated, 89 untreated), 258 (187 treated, 71 untreated), and 106 (74 treated, 32 untreated) patients, respectively. Exposure to AADs was associated with an increased risk of HCC and DC in the unadjusted Cox model (HR: 2.77) and (HR: 3.83), respectively. After adjustment, exposure to AADs was associated with a reduction in overall mortality (HR: 0.48; 95% CI: [0.33–0.70]), HCC (HR: 0.66 [0.46–0.93]), and was no longer associated with CD (HR: 1.14 [0.57–2.27]). Conclusion - In patients with chronic HCV infection, treatment with DAAs is associated with a reduced risk of mortality and HCC. (This article is an adaptation of the following article, published in The Lancet: Carrat F, Fontaine H, Dorival C, Simony M, Diallo A, Hezode C, et al. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: A prospective cohort study. Lancet 2019;393:1453-64).