Objective: This paper describes the multisite, longitudinal cluster randomized controlled trial (RCT) design of the evaluation of the Dating Matters: Strategies to Promote Healthy Relationships initiative, and discusses challenges faced in conducting this evaluation. Method: Health departments in 4 communities are partnering with middle schools in high-risk, urban communities to implement 2 models of teen dating violence (TDV) prevention over 4 years. Schools were randomized to receive either the Dating Matters comprehensive strategy or the “standard of care” strategy (an existing, evidence-based TDV prevention curriculum). Our design permits comparison of the relative effectiveness of the comprehensive and standard of care strategies. Multiple cohorts of students from 46 middle schools are surveyed in middle school and high school, and parents and educators from participating schools are also surveyed. Results: Challenges discussed in conducting a multisite RCT include site variability, separation of implementation and evaluation responsibilities, school retention, parent engagement in research activities, and working within the context of high-risk urban schools and communities. We discuss the strengths and weaknesses of our approaches to these challenges in the hopes of informing future research. Conclusions: Despite multiple challenges, the design of the Dating Matters evaluation remains strong. We hope this paper provides researchers who are conducting complex evaluations of behavioral interventions with thoughtful discussion of the challenges we have faced and potential solutions to such challenges. (PsycINFO Database Record (c) 2016 APA, all rights reserved)