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There is increasing concern about hepatitis C virus (HCV) and potential HIV transmission among ethnic Vietnamese injecting drug users (IDUs) in Australia. To date ethnic and cultural differences in vulnerability to blood-borne viruses (BBV) have received little attention and few studies have attempted to explore the role of cultural beliefs and values in influencing injection risk behaviour. This study aimed to systematically explore the cultural beliefs and behavioural practices that appear to place ethnic Vietnamese IDUs at increased risk of BBV infection, identify barriers to this group accessing health and preventive programs, and document antibody HIV and HCV prevalence and associated risk behaviours. The first component of the research consisted of an ethnographic study designed to explore underlying explanatory models of health and illness employed by Vietnamese IDUs and identify cultural influences on risk behaviours and vulnerability to BBVs. These data were subsequently used to inform the development of the instrument used in the second component – a cross-sectional survey and collection of capillary blood samples designed to assess risk behaviours and antibody HIV and antibody HCV prevalence. Analysis of data from both components indicates that cultural beliefs and practices influence risk-taking and health-seeking behaviours and suggests pathways through which this influence occurs. Relevant cultural characteristics include those pertaining to spiritual and religious beliefs, the role of the family and traditional Vietnamese family values, cultural scripts of self-control and stoicism, the importance of “face” and non-confrontational relationships, trust and obligation, and a reluctance to discuss problems with outsiders. Vulnerability to BBVs is influenced by these cultural characteristics, together with Vietnamese IDUs’ perceptions of risk, knowledge about HIV and HCV, and situational and environmental factors. Main factors contributing to the under-utilisation of health services include the use of self-managed care practices, ambivalence surrounding Western medicine, long waiting times, concerns in relation to confidentiality, stigmatisation of drug use, and limited knowledge of BBVs. The data indicate a need for interventions based on understanding of culturally specific meanings and contexts of health, illness and risk in order to better meet the needs of this vulnerable group.