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Evidence on ‘what works’ to promote women’s economic empowerment has expanded in recent years but remains geographically unbalanced, with English speaking countries and those with more longstanding research traditions better represented. Recognizing the importance of context specificity in understanding and advancing gender equality, we seek to fill a gap in the literature by reviewing interventions, policies, and broader socio-economic trends within West Africa and the extent to which they have contributed to progress in narrowing economic gender gaps in the region. We begin by presenting a conceptual framework for ‘women’s economic empowerment,’ and apply this framework to the West African context, pointing to key binding constraints and enabling conditions to improve women and girls’ economic opportunities and outcomes. We then systematically review the rigorous evidence on what works to promote different dimensions of economic empowerment in West African countries with a focus on three key populations: agricultural workers, entrepreneurs, and adolescent girls/young women. In doing so, we pay particular attention to the heterogeneity in the situation of women and girls based on income, education, marital status, household structure, and other demographic characteristics. Next, we review ongoing investments and initiatives of major multilateral and bilateral donors seeking to expand women’s economic opportunities and empowerment in the region, explore how these investments align with the evidence on ‘what works,’ and identify specific research opportunities these initiatives offer. Finally, we summarize practical research questions, including those that may help address the economic consequences of the COVID-19 pandemic for women and girls.