To ensure that the Comprehensive Osteopathic Medical Licensing Examination- USA (COMLEX-USA) reflects the evolving practice of osteopathic medicine, the National Board of Osteopathic Medical Examiners has developed new content and format specifications for an enhanced, competency-based examination program to be implemented with COMLEX-USA Level 3 in 2018. This article summarizes the evidence-based design processes that served as the foundation for blueprint development and the evidence supporting its validity. An overview is provided of the blueprint’s 2 dimensions: Competency Domains and Clinical Presentations. The authors focus on the evidence that supports interpretation of test scores for the primary and intended purpose of COMLEX-USA, which is osteopathic physician licensure. Important secondary uses and the educational and catalytic effect of assessments are also described. This article concludes with the National Board of Osteopathic Medical Examiners’ plans to ensure that the COMLEX-USA series remains current and meets the needs of its stakeholders—the patients who seek care from osteopathic physicians.