The purpose of this quantitative, predictive correlational study was to investigate the relationship between leader self-efficacy, emotional intelligence, years of experience, and transformational leadership practices of physician assistant (PA) program directors. This study is important in providing a greater understanding of the internal determinants and factors that influence the program directors’ beliefs in their success and effectiveness as leaders. Participants for this study included a sample of 86 PA program directors across the United States. Data were collected using the Leader Efficacy Questionnaire, Wong and Law Emotional Intelligence Scale, Leadership Practices Inventory, and a demographic questionnaire administered via a survey. Multiple linear regression was used to examine the predictive relationship between the variables. The findings revealed that there was a statistically significant predictive relationship between transformational leadership practices and the linear combination of leader self-efficacy, emotional intelligence, and years of experience. This study’s findings can be used to develop more targeted professional development to enhance PA program directors’ leadership effectiveness. Recommendations for future research include conducting qualitative research to gain a deeper understanding of program directors’ use of transformational leadership, examining other demographic variables as predictors, and replicating the study in other health professions programs.