Much of global health research occurs against the backdrop of severe, intersectional and structural vulnerabilities, where susceptibility to disease and early death are driven by poverty, and related factors such as political conflict and climate change. Global health research priorities over the last two decades have been shaped by a small number of high income country institutions, with political commitments informed largely by the ‘global burden of disease’ model. On this model, international research has primarily targeted infectious diseases and other causes of high morbidity and premature, preventable mortality, but has ignored the structural determinants of those diseases. An unintended consequence is that researchers at the frontlines of data collection and interaction with participants and communities come face-to-face with the daily suffering of participants and family members. They often face heart-rending dilemmas in responding to complex health, social, and economic needs that far outstrip the resources and expertise of most research projects or clinical trials. In this presentation, I will share findings from a longitudinal research ethics study, where local ethics teams were embedded within ongoing clinical and social science research studies in contexts of severe poverty, food shortages, droughts and flooding, gender-based violence and political conflict—typical of many global health research sites. Based on our empirical ethics findings, including experiences of research participants, community members and researchers, I will offer critical reflections on the limitations of current accounts of researcher responsibility (ancillary care or duty of care), and suggest we rethink the ways that current global health research institutions and funders engage the underlying structural drivers of disease and suffering.