Background . Chronic stress among medical students affects academic performance of students and leads to depression, substance use, and suicide. There is, however, a shortage of such research evidence in Ethiopia. Objective . We aimed to estimate the prevalence and severity of stress and its association with substance use and academic performance among medical students. Methods . A cross-sectional survey was conducted on a sample of 329 medical students at Jimma University. Data were collected using the General Health Questionnaire (GHQ-12), Medical Students Stress Questionnaire (MSSQ-20), and Drug Abuse Surveillance Test (DAST). Data were analyzed using SPSS version 20.0. Logistic regression analysis and Student’s t-test were applied. Results . The mean age of the respondents was 23.02 (SD = 2.074) years. The current prevalence of stress was 52.4%. Academic related stressor domain was the main source of stress among 281 (88.6%) students. Stress was significantly associated with khat chewing [AOR = 3.03, 95% CI (1.17, 7.85)], smoking [AOR = 4.55, 95% CI (1.05, 19.77)], and alcohol intake [AOR = 1.93, 95% CI (1.03, 3.60)]. The prevalence of stress was high during the initial three years of study. Stress was significantly (p=0.001) but negatively (r=-0.273) correlated with academic achievement. Conclusion . Stress was a significant problem among medical students and had a negative impact on their academic performance. Year of study, income, and substance use were associated with stress. Counseling and awareness creation are recommended.

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