Many Low and Middle Income Countries (LAMICs) still lack sufficient health research capacity to build a local evidence-base with which to inform policy and improve population health. Recognising this, The 2013 World Health Report called for all nations to be producers of health research. To achieve this, new strategies that can develop sustainable locally-led capacity are required. Among the health research capacities needed, ability to conduct clinical trials is important. However, there is no evidence-informed guidance on the best ways to develop locally-led trial capacity. This thesis aims to fill this gap. Three cases-studies using qualitative methods to explore the barriers and enablers to locally-led trial conduct were conducted in Ethiopia, Cameroon and Sri Lanka. Current and potential local trial researchers and health research system stakeholders were recruited. A synthesis of the health research capacity development literature was conducted to compare the case-studies’ findings with wider published perspectives. These data permit an examination of the key issues facing the development of locally-led trial capacity in LAMICs. Barriers and enablers to locally-led trial conduct were found at macro, institutional and individual levels. Although different country research systems, and institutions and individuals within them, were variably successful at conducting trials, the key issues and mechanisms influencing successful trial undertaking were largely similar. Agreement among the case-studies and with the diverse literature suggests that many of the findings will be transferable to other LAMICs, and are also of relevance to other health research methods. A conceptual framework explaining the antecedents and consequences of locally-led trial undertaking in LAMICS is presented. This identifies the following factors as important for supporting locally-led trial undertaking: awareness and appreciation for health research and clinical trials; motivation to conduct clinical trials; availability of human resources with trial knowledge and technical skills; research leadership capabilities; ability to form collaborations, effective teams and acquire resources; trial management dedicated to sustainable capacity development and producing useful research; and system-wide prioritisation of health research. The theories of change presented within this framework are used to develop practical recommendations for development of locally-led trial capacity in LAMICs. These recommendations have four inter-related goals: fostering pro-research cultures in stakeholder institutions; developing trial leaders and staff; providing a facilitative operational environment for trials; and ensuring trial research has an impact. However, to create the will to enact change, advocacy from research champions and conducting trials in a way that benefits local institutions and population health is needed.