In recent years there has been a growth in the number of independent health policy analysis institutes in low- and middle-income countries which has occurred in response to the limitation of government analytical capacity and pressures associated with democratization. This study aimed to: (i) investigate the contribution made by health policy analysis institutes in low- and middle-income countries to health policy agenda setting, formulation, implementation and monitoring and evaluation; and (ii) assess which factors, including organizational form and structure, support the role of health policy analysis institutes in low- and middle-income countries in terms of positively contributing to health policy. Six case studies of health policy analysis institutes in Bangladesh, Ghana, India, South Africa, Uganda and Vietnam were conducted including two NGOs, two university and two government-owned policy analysis institutes. Case studies drew on document review, analysis of financial information, semi-structured interviews with staff and other stakeholders, and iterative feedback of draft findings. Some of the institutes had made major contributions to policy development in their respective countries. All of the institutes were actively engaged in providing policy advice and most undertook policy-relevant research. Relatively few were engaged in conducting policy dialogues, or systematic reviews, or commissioning research. Much of the work undertaken by institutes was driven by requests from government or donors, and the primary outputs for most institutes were research reports, frequently combined with verbal briefings. Several factors were critical in supporting effective policy engagement. These included a supportive policy environment, some degree of independence in governance and financing, and strong links to policy makers that facilitate trust and influence. While the formal relationship of the institute to government was not found to be critical, units within government faced considerable difficulties.