PROJECT SUMMARY Each year, cancer centers invest millions of dollars into “intramural trials”—institutional clinical trials funded to complement larger scale cooperative group, industry, and NIH-funded trials. While clinical trials improve patient care and advance science, our research shows 1 in 5 clinical trials fail to reach their anticipated endpoints, and an additional 1 in 3 do not reach enrollment goals. These failure rates appear higher for smaller and single-center (i.e., more likely intramural) trials. Other than identifying past failure rates, actionable insights to improve trial implementation are lacking, failing both patients and science. In a novel application of implementation science methods, we intend to address this clear gap by adapting existing methodology to the clinical trials context. This innovative approach considers clinical trials as complex interventions with poor implementation. This will provide a platform to study and improve both the science and practice of clinical trials. Guided by Proctor’s implementation outcomes, we will convene a panel of stakeholders to define implementation and other outcomes for intramural clinical trials. This approach will provide institutional and investigator perspectives to inform a conceptual model of intramural trial implementation and success. We will additionally identify determinants of intramural clinical trial outcomes by using the Consolidated Framework for Implementation Research for in-depth and qualitative analysis of intramural clinical trials. Through this study, we will develop foundational methods within a manageable model of the trials enterprise to provide valuable insights to intramural programs and guide future systematic investigation and improvement efforts.