The Merck Childhood Asthma Network, Inc. (MCAN) initiative selected five sites that had high asthma burden and established asthma programs but were ready for greater program integration across schools, health care systems, and communities. MCAN supported a community-based approach that was tailored to the needs of each program site. As a result, each site was unique in its combination of interventions, but all sites served common goals of integration of care, incorporation of evidence-based programs, and improvement in knowledge, self-management, health, and quality of life. This case study of the MCAN cross-site evaluation discusses the challenges associated with evaluating interventions involving multiple stakeholders that have been adjusted to fit the unique needs of specific communities. The evaluation triangulates data from site-specific monitoring and evaluation data; site documents, site visits, and cross-site meetings; qualitative assessments of families, organizational partners, and other stakeholders; and quantitative data from a common instrument on health indicators before and after the intervention. The evaluation employs the RE-AIM framework—reach, effectiveness, adoption, implementation, and maintenance—to assess the barriers and facilitators of translation from theory into practice. Our experience suggests trade-offs between rigor of evaluation and burden of assessment that have applicability for other community-based translational efforts.