Excellence in physical therapy (PT) education is an essential component in meeting the evolving needs of this rapidly growing profession. In PT education, the National Physical Therapy Examination (NPTE) continues to be the predominant outcome indicator of student success. Passing the NPTE assumes that PT students’ academic and clinical competencies were achieved, and therefore, that exam serves as the PT professions “gatekeeper” as to who can be licensed to practice. As a high-stakes examination, predicting NPTE performance is important for PT students, faculty, and programs. The purpose of the present study was to determine the empirical relationships of NPTE performance for each of the PT applicant and PT student variables identified from a systematic literature review. The current investigation utilized a systematic literature review with a subsequent random effects meta-analysis to determine the empirical relationships between PT applicant variables and PT student variables with NPTE performance. Findings indicated that all of the PT applicant variables had a moderate effect size and significant relationship with NPTE performance, with undergraduate grade point averages of prerequisite courses (UGPA PC) having the largest relationship with NPTE performance. Four of the PT student variables (first-year PTGPA, overall PTGPA, Nelson Dennehy Reading Test scores, and comprehensive exam scores) had a large effect size and statistically significant relationship NPTE performance. The remaining PT student variables (which includes the clinical performance scores from the first and the final clinical experiences) all had weak relationships with NPTE performance. The results from the present study provides evidence for the implementation of a comprehensive approach for admission into a professional program in PT. Further, the first-year PTGPA should be assessed to identify those who are at a risk of failing the NPTE on their first-attempt. Most notably, the results from the random effects meta-analysis for the clinical performance scores (both first and final clinical experiences) raise concerns that the NPTE may not be adequately assessing individual PT students’ clinical learning and performance, indicating that PT educators should review the current model of PT student assessment.