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Background: The rise of non-communicable diseases (NCDs) in Africa requires a multi-sectoral action (MSA) in their prevention and control. This study aimed to generate evidence on the extent of MSA application in NCD prevention policy development in five sub-Saharan African countries (Kenya, South Africa, Cameroon, Nigeria and Malawi) focusing on policies around the major NCD risk factors.Methods: The broader study applied a multiple case study design to capture rich descriptions of policy contents, processes and actors as well as contextual factors related to the policies around the major NCD risk factors at single- and multi-country levels. Data were collected through document reviews and key informant interviews with decision-makers and implementers in various sectors. Further consultations were conducted with NCD experts on MSA application in NCD prevention policies in the region. For this paper, we report on how MSA was applied in the policy process.Results: The findings revealed some degree of application of MSA in NCD prevention policy development in these countries. However, the level of sector engagement varies across different NCD policies, from passive participation to active engagement, and by country. There was higher engagement of sectors in developing tobacco policies across the countries, followed by alcohol policies. Multi-sectoral action for tobacco and to some extent, alcohol, was enabled through established structures at national levels including inter-ministerial and parliamentary committees. More often coordination was enabled through expert or technical working groups driven by the health sectors. The main barriers to multi-sectoral action included lack of awareness by various sectors about their potential contribution, weak political will, coordination complexity and inadequate resources.Conclusion: MSA is possible in NCD prevention policy development in African countries. However, the findings illustrate various challenges in bringing sectors together to develop policies to address the increasing NCD burden in the region. Stronger coordination mechanisms with clear guidelines for sector engagement are required for effective MSA in NCD prevention. Such a mechanisms should include approaches for capacity building and resource generation to enable multi-sectoral action in NCD policy formulation, implementation and monitoring of outcomes. [ABSTRACT FROM AUTHOR]