BackgroundSelf-medication among university students is becoming a health concern, especially during examinations and stress. This pattern of medication use among students could lead to adverse health consequences if it is not addressed and tackled. Thus, this study investigated the most associated factors with this practice among students. MethodsAn observational cross-sectional study was conducted among university students in Northern Borders Province, Saudi Arabia. A total of 220 students were selected and took part in the survey. Data was collected through a self-administered questionnaire. The survey was distributed among participants to answer five sections: demographic and socioeconomic characteristics, health status problems, satisfaction with academic performance, and self-medication questions. The content validity was tested using a pilot sample of 30 students. The descriptive, univariate, and multivariate analyses were conducted using the Statistical Package for Social Science program. ResultsIn the present sample of university students, the response rate was 100%. Approximately one-third reported using medications without prescriptions, and 83% of them have used medications three times at most during the past 12 months. Headache was the most common reason for use (59%), followed by fever (20%). Adjusted multivariate analysis showed that students who were 21–24 years of age (OR = 3.79, 95% CI = 1.21–11.82), female (OR = 2.43, 95% CI = 1.03–5.72), and living alone in private housing (OR = 3.62, 95% CI = 1.32–9.90) were at high risk of self-medication as compared to their counterparts. However, students in the last years of college (fourth (OR = 0.14, 95% CI = 0.03–0.62), fifth (OR = 0.21, 95% CI = 0.05–0.95), sixth (OR = 0.05, 95% CI = 0.01–0.35)) were at lower risk as compared to their counterparts. ConclusionThe study found that self-medication was common among university students, with higher rates among those who were 21–24 years old, female, and living alone in private housing, but lower rates among students in the later years of college. Educational programs and awareness campaigns should target students who are at higher risk of practicing self-medication to avoid misuse of over-the-counter medications.