Introduction The high prevalence of hepatitis C and the persistence of HIV and hepatitis C virus (HCV) risk practices in people who inject drugs (PWID) in France underlines the need for innovative prevention interventions. The main objective of this article is to describe the design of the COSINUS cohort study and outline the issues it will explore to evaluate the impact of drug consumption rooms (DCR) on PWID outcomes. Secondary objectives are to assess how DCR (a) influence other drug-related practices, such as the transition from intravenous to less risky modes of use, (b) reduce drug use frequency/quantity, (c) increase access to treatment for addiction and comorbidities (infectious, psychiatric and other), (d) improve social conditions and (e) reduce levels of violence experienced and drug-related offences. COSINUS will also give us the opportunity to investigate the impact of other harm reduction tools in France and their combined effect with DCR on reducing HIV-HCV risk practices. Furthermore, we will be better able to identify PWID needs. Methods and analysis Enrollment in this prospective multi-site cohort study started in June 2016. Overall, 680 PWID in four different cities (Bordeaux, Marseilles, Paris and Strasbourg) will be enrolled and followed up for 12 months through face-to-face structured interviews administered by trained staff to all eligible participants at baseline (M0), 3 month (M3), 6 month (M6) and 12 month (M12) follow-up visits. These interviews gather data on socio-demographic characteristics, past and current drug and alcohol consumption, drug-use related practices, access to care and social services, experience of violence (as victims), offences, other psychosocial issues and perception and needs about harm reduction interventions and services. Longitudinal data analysis will use a mixed logistic model to assess the impact of individual and structural factors, including DCR attendance and exposure to other harm reduction services, on the main outcome