BackgroundDespite improvements over time, West Africa lags behind global as well as sub-Saharan averages in its maternal, newborn and child health (MNCH) outcomes. This is despite the availability of an increasing body of knowledge on interventions that improve such outcomes. Beyond our knowledge of what interventions work, insights are needed on others factors that facilitate or inhibit MNCH outcome improvement. This study aimed to explore health system factors conducive or limiting to MNCH policy and programme implementation and outcomes in West Africa, and how and why they work in context.MethodsWe conducted a mixed methods multi-country case study focusing predominantly, but not exclusively, on the six West African countries (Burkina Faso, Benin, Mali, Senegal, Nigeria and Ghana) of the Innovating for Maternal and Child Health in Africa initiative. Data collection involved non-exhaustive review of grey and published literature, and 48 key informant interviews. We validated our findings and conclusions at two separate multi-stakeholder meetings organised by the West African Health Organization. To guide our data collection and analysis, we developed a unique theoretical framework of the link between health systems and MNCH, in which we conceptualised health systems as the foundations, pillars and roofing of a shelter for MNCH, and context as the ground on which the foundation is laid.ResultsA multitude of MNCH policies and interventions were being piloted, researched or implemented at scale in the sub-region, most of which faced multiple interacting conducive and limiting health system factors to effective implementation, as well as contextual challenges. Context acted through its effect on health system factors as well as on the social determinants of health.ConclusionsTo accelerate and sustain improvements in MNCH outcomes in West Africa, an integrated approach to research and practice of simultaneously addressing health systems and contextual factors alongside MNCH service delivery interventions is needed. This requires multi-level, multi-sectoral and multi-stakeholder engagement approaches that span current geographical, language, research and practice community boundaries in West Africa, and effectively link the efforts of actors interested in health systems strengthening with those of actors interested in MNCH outcome improvement.