To identify barriers to stakeholder alignment and strategies used by 14 multi-stakeholder alliances participating in the Aligning Forces for Quality initiative to overcome these barriers. The study used a mixed method, comparative case study design. Alliances were categorized as more or less highly aligned based on an alignment index constructed from survey responses. Six alliances (top and bottom quartile) were selected for more in-depth qualitative analysis. Semi-structured interviews of key informants were used to identify factors that distinguished more highly aligned alliances from less highly aligned alliances. Market context was one of the most important factors differentiating alliances. More highly aligned alliances had more extensive histories of collaboration, established more credibility in the local community, and were more effective at balancing collaborative initiatives against competitive interests. More highly aligned alliances also took more active approaches to build consensus among stakeholders regarding alliance initiatives, and were able to successfully utilize small decision-making bodies to foster this consensus. In contrast, leadership credibility, leadership stability, and trust were important facilitators of alignment for all alliances, regardless of the level of alignment. These factors intersect and overlap in a multitude of ways to influence stakeholder alignment. Alignment in an alliance context is critical for leveraging the unique knowledge, skills, and abilities of stakeholders in ways that can build capacity to improve the health of the community in ways that cannot be achieved independently by stakeholders. The findings highlight the need for multifaceted approaches to promote stakeholder alignment.