INTRODUCTION: Hepatitis C virus (HCV) represents a serious public health concern. People who inject drugs (PWID) are at particular risk and nearly half (45%) of PWID in England may be infected. HCV prevention interventions have only had moderate impact on the prevalence of HCV in this population. Using qualitative methods, we sought to detail the protective practices potentially linked to HCV avoidance among PWID, and explore the motivations for these. METHODS: The study used a life history approach allowing participants to detail their lived experience both before and during the course of their injecting careers. Thirty-seven participants were recruited from drug services in London, and from referrals within local injecting networks. A baseline and follow-up in-depth qualitative interview was carried out with each participant, and for half, a third interview was also undertaken. All underwent testing for HCV antibody. Analyses focused on developing a descriptive typology of protective practices potentially linked to HCV avoidance. RESULTS: Practices were deemed to be protective against HCV if they could be expected a priori to reduce the number of overall injections and/or the number of injections using shared injecting equipment. Participants reported engaging in various protective practices which fell into three categories identified through thematic analysis: principles about injecting, preparedness, and flexibility. CONCLUSIONS: All participants engaged in protective practices irrespective of serostatus. It is important to consider the relative importance of different motivations framing protective practices in order to formulate harm reduction interventions which appeal to the situated concerns of PWID, especially given that these protective practices may also help protect against HIV and other blood borne infections.