Non-suicidal self-injury is a significant health problem among adolescents and college students. Self-injury is often used as a negative method of coping with adverse emotions and psychological distress. Therefore, the purpose of this study is to examine past year self-injury and potential associated factors such as substance use and mental health. A total of 777 students completed the American College Health Association—National Health Assessment Survey II in classrooms. Logistic regression analysis was used to examine the study aims. Results indicated 7.0% of students reported past year self-injury. Logistic regression analysis revealed significant differences based on grade, relationship status, abuse, substance use, and mental health problems. The final model significantly predicted past year self-injury and accounted for 19%–48% of the variance in past year self-injury. In the final model, students who seriously considered suicide were greater than six times more likely to self-injure and students who attempted suicide were greater than 16 times more likely to self-injure. It appears prevention and intervention programs for college students are needed. College health professionals and others working with students may seek to identify high-risk groups for further intervention. Students with a history of considering suicide and suicide attempts may be at highest risk. Providing additional support to such students may reduce the risk of self-injury.