The Comprehensive Osteopathic Medical Licensing Examination-USA (COMLEX-USA) assesses the competence of osteopathic physicians in training. It is designed to protect the public by setting minimum competence standards. All osteopathic medical students must pass COMLEX-USA Level 1, Level 2-Cognitive Evaluation, and Level 2-Performance Evaluation before being allowed to graduate from an osteopathic medical school. Residency training programs use COMLEX-USA scores as a major factor in deciding whom they will interview and admit into their programs. In addition, colleges of osteopathic medicine use student COMLEX-USA scores as an external assessment of their success in educating students. Because COMLEX-USA is a high-stakes examination series, it is important to understand predictive factors for performance. The authors review the literature on the relationship between COMLEX-USA scores and correlated student variables. Results from the Council on Osteopathic Student Government Presidents' survey on students' preparation methods and performance are also provided.