Among treatment-naïve individuals with chronic HCV infection and without cirrhosis, glecaprevir-pibrentasvir for eight weeks is recommended. The aim of this analysis was to evaluate the efficacy of glecaprevir-pibrentasvir for six weeks in people with acute and recent HCV infection. In this open-label single-arm multicentre international pilot study, adults with recent HCV (duration of infection <12 months) received glecaprevir-pibrentasvir 300mg-120mg daily for six weeks. Primary infection was defined by first positive anti-HCV antibody and/or HCV RNA within six months of enrolment and either acute clinical hepatitis within the past 12 months (symptomatic seroconversion illness or ALT>10xULN) or anti-HCV antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within six months of enrolment and evidence of prior spontaneous or treatment-induced clearance. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12). Thirty men (median age 43 years, 90% men-who-have-sex-with-men) received treatment, of whom 77% (n=23) were HIV-positive, 47% (n=14) had ever injected drugs, and 13% (n=4) had HCV reinfection. The majority had HCV genotype 1 (83%, n=25), followed by genotype 4 (10%, n=3) and genotype 3 (7%, n=2). At baseline, median estimated duration of infection was 29 weeks (range 13, 52) and median HCV RNA was 6.2 log10 IU/mL (range 0.9, 7.7). SVR12 in the intention-to-treat and per-protocol populations was achieved in 90% (27/30) and 96% (27/28), respectively. There was one case of relapse and two cases of non-virological failure (death, n=1; loss to follow up, n=1). No treatment-related serious adverse events were seen. CONCLUSION: Glecaprevir-pibrentasvir for six weeks was highly effective among people with acute and recent HCV infection, supporting further evaluation of shortened duration pan-genotypic therapy in this setting. © 2019 by the American Association for the Study of Liver Diseases.