This Guide provides focused documentation to assist users of NextGen software to improve the process of assessing, documenting, tracking, and following up on colorectal cancer screening. The Guide gives particular attention to assessment of personal and family risk and the tracking and follow-up of screening results that are not addressed in the standard NextGen guidance documents. This work aims to improve health center compliance with HRSA Uniform Data Systems (UDS) colorectal cancer screening (CRCS) through the development and implementation of workflows that produce accurate and reliable structured data and enable proactive outreach and timely follow-up with patients due for CRCS or follow-up testing. This optimization enables health centers to harness broader evidence-based strategies to improve CRCS compliance, and ultimately, health outcomes.