ABSTRACT: BACKGROUND:Sub-Saharan Africa has a large population of people with hepatitis C virus (HCV) infection, yet little is known about HCV among people who inject drugs this region. We assessed the prevalence of HCV mono-infection and HIV-HCV co-infection, and the estimated incidence, genotypes, and risk behaviours associated with HCV among people who inject drugs in Kenya. METHODS:People aged 18 years or older who were living in Nairobi, coastal Kenya, or western Kenya, had a history of injection drug use, and had used any illicit drugs in the past 12 months were recruited at needle and syringe programme sites using respondent-driven sampling. Participants were screened for the presence of an anti-HCV antibody. Those who were anti-HCV positive underwent confirmatory HCV RNA testing, and those with detectable HCV RNA were genotyped. Participants were interviewed regarding parenteral risk behaviours and exposure to services received at the needle and syringe programme sites. We examined correlates of HCV infection and HIV-HCV co-infection using bivariate and multivariate regression, and estimated HCV incidence. FINDINGS:Of 2188 enrolled participants, 291 (13%) were anti-HCV positive: 183 (22%) of 842 participants in coastal Kenya, 105 (13%) of 817 in Nairobi, and three (1%) of 529 in western Kenya. 284 anti-HCV-positive participants underwent successful HCV RNA testing, of whom 230 (81%) were viraemic. Estimated incidence rates of anti-HCV positivity per 100 person-years were 6·31 in coastal Kenya, 3·19 in Nairobi, and 0·22 in western Kenya. HCV incidence rate was greater in coastal Kenya compared with Nairobi (incidence rate ratio 1·97 [95% CI 1·35-2·93], p=0·0001) and the western region (28·17 [7·55-236·58], p<0·0001). In the coastal region, history of incarceration, more years injecting, more injections in the past month, and receptive cooker sharing were associated with increased risk of HCV, while female sex, more years injecting, more injections in the past month, and regular use of a syringe with a detachable needle were associated with HCV risk in Nairobi. HCV prevalence among HIV-positive participants was 50% (66 of 131 participants) in coastal Kenya, 35% (42 of 121) in Nairobi, and 4% (one of 23) in western Kenya. Risk factors for HIV-HCV co-infection were similar to those observed for HCV mono-infection. The prevailing genotypes were 1a (51%), 4a (47%), and mixed (2%; three 1a/4a and one 1a/2b). INTERPRETATION:HCV prevalence, estimated incidence, and risk behaviours among people who inject drugs in Kenya vary with region, with the highest estimated incidence observed in coastal Kenya. These findings should be used to inform focused strategies to reduce HCV transmission, such as expansion of needle and syringe programmes, upscaling of opioid agonist therapy, and treatment as prevention in regions affected by injection drug use and HCV. FUNDING:National Institute on Drug Abuse.