Background: Aboriginal and Torres Strait Islander people experience inequity in health outcomes in Australia. Health care interactions are an important starting place to seek to address this inequity. The majority of health professionals in Australia do not identify as Aboriginal and/or Torres Strait Islander people and the health care interaction therefore becomes an example of working in an intercultural space (or interface). It is therefore critical to consider how health professionals may maximise the positive impact within the health care interaction by skilfully working at the interface. Methods: Thirty-five health professionals working in South Australia were interviewed about their experiences working with Aboriginal people. Recruitment was through purposive sampling. The research was guided by the National Health and Medical Research Council Values and Ethics for undertaking research with Aboriginal communities. Critical social research was used to analyse data. Results: Interviews revealed two main types of factors influencing the experience of non-Aboriginal health professionals working with Aboriginal people at the interface: the organisation and the individual. Within these two factors, a number of sub-factors were found to be important including organisational culture, organisational support, accessibility of health services and responding to expectations of the wider health system (organisation) and personal ideology and awareness of colonisation (individual). Conclusions: A health professional's practice at the interface cannot be considered in isolation from individual and organisational contexts. It is critical to consider how the organisational and individual factors identified in this research will be addressed in health professional training and practice, in order to maximise the ability of health professionals to work with Aboriginal and Torres Strait Islander people and therefore contribute to addressing health equity.