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REACH is an empirical research ethics study in global health, now in its fourth and final year. In this project we set out to address important gaps in research ethics guidance for those working with vulnerable populations in low resource, high disease burden settings typical of much of global health research. At the heart of the study are six qualitative case studies, where our bioethics teams were linked to or embedded within ongoing clinical research studies in coastal Kenya, KwaZulu-Natal, South Africa, and in the rural border regions of Thailand. The bioethics teams engaged research teams throughout daily research over time, to better understand what ethical issues arise along the typical research pathway—from study design, to post-study activities. We also engaged research participants and community members to better understand experiences of daily challenges in their own words, sources of specific vulnerabilities, sources of support, and how these manifested in research participation. Findings across these diverse sites help illuminate significant blind spots in how research ethics has traditionally thought of ‘vulnerability’ as an ethical concept, with implications for the practical ethical obligations of researchers working in low resource settings. We will share highlights on behalf of our team, including implications for how we think about ancillary care duties, moral distress, research benefits, and the intersectional nature of vulnerability and respect for agency. We will also offer reflections on the ethical role of research in low income settings—including its purpose and limits as a substitute for health systems development or humanitarian interventions.