Purpose: To understand the dynamic capabilities that enabled the six demonstration projects of the Information Technology Networks of Care Initiative to implement health information exchanges (HIEs) tailored to their local HIV epidemics and regional care systems. Methods: We conducted 111 semi-structured interviews with project staff and information technology (IT) specialists associated with the demonstration projects, staff from community-based organizations and public health agencies collaborating in the design and implementation of the HIEs, and providers who used each HIE. The dynamic capability framework guided analyses. In the context of a HIE, the framework's components include information systems (the actual technological exchange systems and capacity to update them), absorptive capacity (the ability to implement an operating HIE), reconfiguration capacity (the ability to adapt workflows and clinical practices in response to a HIE), and organizational size and human resources (characteristics likely to affect a clinic's ability to respond). Results: Across the projects, we found evidence for the importance of three dynamic capabilities: information systems, reconfiguration capacity, and organizational size and human resources. However, of these three, reconfiguration capacity was the most salient. Implementation outcomes at all six of the projects were shaped substantially by the degree of attention dedicated to reworking procedures and practices so that HIE usage became routine. Conclusion: Electronic information exchange offers the promise of improved coordination of care. However, implementation of HIEs goes beyond programing and hardware installation challenges, and requires close attention to the needs of the HIEs end-users. Providers need to discern value from a HIE because their active participation is essential to ensuring that clinic and agency practices and procedures are reconfigured to incorporate new systems into daily work processes. © 2012 Elsevier Ireland Ltd.