Research suggests that students entering their first year of college may be at significant risk for developing substance use problems by relying on substances to regulate their emotions. Objective: The aim of the current study was to examine the dual role of personality and psychopathology in predicting substance use among first-year students. Participants: 103 first-semester undergraduate students were recruited via the university subject pool. Methods: Participants completed personality questionnaires, structured clinical interviews, followed by the completion of diary entries each week reporting on substance use throughout their first semester. Results: Results indicated that a past diagnosis of an affective (mood/anxiety/stress) disorder was the most significant predictor of substance use. Personality and current psychopathology had no association to substance use. past Conclusion: This finding is consistent with developmental models of substance use relating to emotion-related disease and suggests that greater nuance is needed in understanding substance use risk in college students.