BACKGROUND: A stakeholders survey in 2018 identified linkage to care (LtC) and adherence to treatment (AtT) as priority areas for inclusion in the updated ECDC/EMCDDA guidance on prevention of infection among people who inject drugs(PWID) (publication planned for early 2022). This systematic review aimed to support guidance update process by identifying interventions that can improve LtC and AtT for infections among PWID. *** METHODS: The protocol, including PICO questions and search strategy, is available at PROSPERO (2020 CRD42020191116). Searches were conducted in PubMed, EMBASE, PsycINFO, Clinical Trials Registry, CDSR to identify studies published during 2011-2020 in EU/EEA/EFTA countries, EU candidate countries, the UK, US, Canada, Australia and New Zeeland. Studies were included if had a comparative study design (e.g. RCT, pre-post intervention comparison) and reported on LtC and or AtT among PWID/people in Opioid Substitution Therapy. Following the risk of bias (EPHPP) and quality of evidence assessment (GRADE), evidence to decision tables were produced and shared for critical review with an expert panel convened by ECDC and EMCDDA. The expert panel provided further considerations on benefit, acceptability and transferability of interventions. *** RESULTS: Of 7318 unique records, 251 were reviewed in fulltext and 20 studies were included in evidence synthesis. Eleven of 20 studies evaluated interventions based on direct-acting antiviral (DAA) therapy and three on both interferon-based and DAA. Evidence indicates that integrated HCV care with case management, peer support, psychological interventions, contingency management, and cooperation between health care providers improves the primary outcomes (LtC: visits, treatment initiation, treatment completion; AtT: treatment adherence, SVR12) in most studies. *** CONCLUSION: Linkage to care of people diagnosed with HCV is pivotal for progressing the elimination efforts. To improve the HCV cascade of care among PWID, interventions should be implemented in combination with harm reduction services, drug treatment and considering the healthcare system characteristics and legal framework.