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Randomized control trials (RCTs) are considered to be the gold standard for impact evaluation in international development and they are associated with a new era of evidence-based global health policies. However, there are inherent challenges in using RCTs to answer some of the most important questions in global health: why, if solutions are known, affordable at scale, and supported by existing evidence, do hundreds of millions of people lack access to essential health services? A lack of clarity on appropriate research methods for strengthening health systems has corresponded to a lack of investment in more complex and adaptive systems of integrated care delivery. This chapter reviews the use of RCTs in global health, highlighting major contributions, and addressing some pressing priorities in implementation research at a time when the Sustainable Development Goals emphasize the importance of sector-wide approaches, such as integrated primary care and universal health coverage.