Many innovations in the health sector are complex, requiring coordinated use by multiple organizational members to achieve benefits. Often, complex innovations are adopted with great anticipation only to fail during implementation. The health services literature provides limited conceptual guidance to researchers and practitioners about implementation of complex innovations. In the present study, we adapt an organizational framework of innovation implementation developed and validated in a manufacturing setting and explore the extent to which it aptly characterizes implementation in health sector organizations. Through comparative case studies of four cancer clinical research networks, we illustrate how this conceptual framework captures key determinants of the implementation of new programs in cancer prevention and control (CP/C) research and helps explain observed differences in implementation effectiveness. Key determinants include management support and innovation-values fit, which contribute to an organizational "climate" for implementation. We explore the implications for researchers and managers.