Background: Designing implementation programs that effectively integrate complex healthcare innovations into complex settings is a fundamental aspect of knowledge translation. We describe the development of a conceptually grounded implementation program for a complex healthcare innovation and its subsequent application in pediatric hospital settings.Methods: We conducted multiple case observations of the application of the Phased Reciprocal Implementation Synergy Model (PRISM) framework in the design and operationalization of an implementation program for a complex hospital wide innovation in pediatric hospital settings.Results: PRISM informed the design and delivery of 10 international hospital wide implementations of the complex innovation, BedsidePEWS. Implementation and innovation specific goals, overarching implementation program design principles, and a phased-based, customizable, and context responsive implementation program including innovation specific tools and evaluation plans emerged from the experience.Conclusion: Theoretically grounded implementation approaches customized for organizational contexts are feasible for the adoption and integration of this complex hospital-wide innovation. Attention to the fitting of the innovation to local practices, setting, organizational culture and end-user preferences can be achieved while maintaining the integrity of the innovation. [ABSTRACT FROM AUTHOR]