The purpose of this study was to identity how events perceived as traumatic or very difficult to handle, factors of emotional distress, and demographics may predict nonmedical use of prescription drugs (NMPD) among traditional undergraduate college students. This secondary analysis utilized data from the National College Health Assessment II (NCHA II) from the Fall 2010 for the primary analysis. Data from the Fall 2008 and 2009 semester were subsequently analyzed to validate results over time. Sequential logistic regression was used to determine NMPD; first evaluating events perceived as traumatic, then including factors of emotional distress, and finally adding demographics of race and ethnicity, gender, Greek affiliation, and year-in-school. Fifth year (58-103%), 4th year (46-67%), 3rd year (43-60%), Greek affiliation (35-55%), feeling suicidal (27-49%), difficulties with intimate relationships (22-46%), males (28-39%), sleep difficulties (14-37%), feeling angry (29-35%), death of a family member or friend (13-29%), 2nd year (25-28%), feeling anxious (18-27%), and difficulties with finances (16-24%) were significantly more likely to predict NMPD during Fall 2008-2010 semesters. Conversely, Asians or Pacific Islanders (70-79%) and Blacks or African Americans (19-40%) were significantly less likely to use prescription drugs nonmedically over the same time period. While statistically significant, the model lacked increase of strength as variables were added to the regression equation. Regardless, college counselors, health professionals, and administrators should target support and interventions to assist students struggling with trauma, emotional distress, and the misuse of prescription drugs.