Background: There is growing interest among funders about how to deliver effective health programmes at scale with finite budgets. While there is a rich conceptual literature on scale-up and diffusion of innovations, few empirical studies have been conducted on health programmes in low-income settings, meaning assumptions about scale-up are largely untested. We present findings from a multi-country qualitative study exploring scale-up of demand and supply-side innovations in maternal and newborn health in Ethiopia, India and Nigeria. The aims are to: (1) identify and understand major factors enabling/inhibiting scale-up of these innovations; (2) evaluate the effectiveness of mechanisms for catalysing and enabling their scale-up. The study is part of IDEAS (Informed Decisions for Actions to improve maternal and newborn health), a five-year measurement, learning and evaluation project led by the London School of Hygiene and Tropical Medicine and funded by the Bill & Melinda Gates Foundation. Methods: We developed a conceptual framework to structure data collection/analysis drawing on diverse disciplinary approaches including the diffusion of innovations literature, health policy analysis, and health systems and services research. In April-September 2012 we will carry out 225 in-depth/semi-structured interviews with government officials, development agencies, private sector stakeholders and civil society. Results: The paper will present study findings based on the 225 interviews. We expect multiple factors to explain (limited) scale-up: attributes of an innovation; decision makers’ political/ideological values and financial interests; capacities of implementers; geographical, economic and sociocultural determinants of community uptake; political, economic, technological, legal and institutional country contexts. We expect different mechanisms for catalysing scale-up to be effective in different settings including policy advocacy and appealing to opinion leaders to spread ideas through community networks. Conclusions: Evidence on scale-up health programmes is needed since concepts/theories remain largely untested.