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PURPOSE The purpose of this study was to evaluate a primary care practice–based quality improvement (QI) intervention aimed at improving colorectal cancer screening rates. METHODS The Supporting Colorectal Cancer Outcomes through Participatory Enhancements (SCOPE) study was a cluster randomized trial of New Jersey primary care practices. On-site facilitation and learning collaboratives were used to engage multiple stakeholders throughout the change process to identify and implement strategies to enhance colorectal cancer screening. Practices were analyzed using quantitative (medical records, surveys) and qualitative data (observations, interviews, and audio recordings) at baseline and a 12-month follow-up. RESULTS Comparing intervention and control arms of the 23 participating practices did not yield statistically significant improvements in patients’ colorectal cancer screening rates. Qualitative analyses provide insights into practices’ QI implementation, including associations between how well leaders fostered team development and the extent to which team members felt psychologically safe. Successful QI implementation did not always translate into improved screening rates. CONCLUSIONS Although single-target, incremental QI interventions can be effective, practice transformation requires enhanced organizational learning and change capacities. The SCOPE model of QI may not be an optimal strategy if short-term guideline concordant numerical gains are the goal. Advancing the knowledge base of QI interventions requires future reports to address how and why QI interventions work rather than simply measuring whether they work.