Objective <p>The primary objective of this study was to assess the relationship between Adverse Childhood Experiences (ACEs) and well-being in medical students and determine if resilience plays a moderating role in this dynamic. A secondary objective was to provide more descriptive data on ACEs as they relate to medical student demographics.</p> Methods <p>The authors administered an anonymous survey to Southeastern US medical students (<i>N</i> = 794) from March to May 2024. The survey included demographics, a 10-item ACE questionnaire, the Brief Resilience Scale, and the Mayo Medical School Well-Being Index.</p> Results <p>Fifty-three medical students (65%) reported at least 1 ACE while 21 students (25%) reported at least 4 ACEs. Females, minorities, and students from low-income families (Pearson correlation coefficient = −&#xa0;.288, <i>P</i> &lt; 0.001) tended to report higher ACE scores. Students with an ACE score of 4 or more were significantly more likely to report a state of distress (chi-square test, <i>P</i> = 0.002) compared to individuals with less than 4 ACEs. While 79% of students endorsed either moderate or high resilience levels, the students with low resilience reported poor well-being significantly more (chi-square test, <i>P</i> &lt; 0.001). A logistic regression test found resilience (<i>P</i> = 0.008) and ACE score (<i>P</i> = 0.011) to be associated with well-being status, but resilience did not significantly moderate the relationship between ACEs and well-being (<i>b</i> = 0.069, <i>P</i> = 0.115).</p> Conclusions <p>A history of ACEs or low resilience in medical students may contribute to poor mental health outcomes in future physicians and, as a result, should be considered a potential risk factor.</p>