Background & aims: Direct-acting antivirals (DAA) lead to high sustained virological response (SVR) rates and decrease the risk of disease progression. We compared SVR rates and all-cause, liver- and non-liver-related deaths, liver-related events, and non-liver-related cancers in HIV/HCV-coinfected and HCV-monoinfected participants from 2 French cohort studies after initiation of DAA treatment. Methods: Up to 4 HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to each HIV/HCV-coinfected patient from the ANRS CO13 HEPAVIH cohort; both are nationwide, prospective, multicentre, and observational. Participants were initiated on DAAs between March 2014 and December 2017. Cox proportional hazards models adjusted by age, sex, duration since HCV diagnosis, HCV transmission routes, HCV genotypes, cirrhosis, tobacco, alcohol consumption, and SVR (time dependent) were used. Results: A total of 592 HIV/HCV-coinfected and 2,049 HCV-monoinfected participants were included; median age was 53.3 years (inter-quartile range: 49.6-56.9) and 52.9 years (49.6; 56.7), 1,498 (73.1%) and 436 (73.6%) were men, and 159 (28.8%) and 793 (41.2%) had cirrhosis, respectively. SVR was observed in 92.9% and 94.6%, respectively. HIV coinfection was associated with higher risk of all-cause death (hazard ratio [HR] 1.93; 95% CI 1.01-3.69), non-liver-related death (HR 2.84; 95% CI 1.27-6.36), and non-liver-related cancer (HR 3.26; 95% CI 1.50-7.08), but not with liver-related-death (HR 1.04; 95% CI 0.34-3.15) or liver-related events (HR 0.66; 95% CI 0.31-1.44). Conclusions: After DAA treatment, HIV-coinfected individuals had similar SVR rates and risk of liver-related deaths and events compared with HCV-monoinfected individuals, but had a higher risk of all-cause and non-liver-related deaths and non-liver-related cancers. Lay summary: We compared the risk of several clinical events in participants infected by human immunodeficiency virus and hepatitis C virus with those infected with hepatitis C virus alone, matched on age and sex, after treatment with contemporary direct-acting antivirals. We found a higher risk of all-cause deaths, non-liver-related deaths, and non-liver-related cancers in participants coinfected with the human immunodeficiency virus and hepatitis C virus, and no differences for the risk of liver-related deaths or events. Trial registration: ClinicalTrials.gov NCT03324633 NCT01953458.< Réduire