While obtaining voluntary informed consent for research participation is an ethical imperative, there appears to be little consensus regarding what constitutes a voluntary consent decision. As a result, considerable controversy exists in the research ethics literature, with researchers and ethicists advancing numerous concerns about the voluntariness of consent to research. However, without a valid conceptualisation of voluntariness and an appropriate means of assessing it, it is impossible to determine whether commonly expressed concerns about voluntariness are well founded. For this reason, a comprehensive review of conceptual and empirical work on voluntary consent to research was conducted. On the basis of this conceptualisation, an instrument to assess influences on participants’ consent decision and perceived voluntariness was developed and piloted in two South African HIV clinical trials. The pilot study found high levels of perceived voluntariness. The feeling of having no choice but to participate was significantly associated with lower perceived voluntariness. An absence of controlling influences from other people was observed for the majority of research participants. The need for health care and trust in the researchers were primary influences on participation. Overall the data suggest that it is possible to obtain voluntary and valid consent for research participants in ethically complex HIV clinical trials in a developing country context.