Some have characterized patients living with intractable pain as a vulnerable population in both clinical and research settings. Labeling the population as vulnerable, however, does not provide clarity regarding the potential risks that they face when they participate in research. Instead, research vulnerability for patients in pain is a function of an interaction between their pain conditions and elements of the research enterprise. Therefore, the identification of potential risks requires consideration not only of characteristics of patients with chronic pain, but also consideration of features of researchers, the quality of institutional oversight, and the medical/social environment within which the research is conducted. This paper provides an analysis of those risks and provides some suggestions as to how the risks might be better managed.