BACKGROUND: Self-medication is a practice with major global implications, especially with antibiotics intake. Self-medication among future health-care professionals could affect their way in prescribing medication in the future. AIM: This study was conducted to estimate the magnitude and the determinants of antibiotics self-medication practices and to describe the pattern of antibiotics abuse among undergraduate university students. METHODS: A cross-section study was conducted among 563 medical students from public and private universities in Cairo, Egypt, using a questionnaire. RESULTS: About 77.7% of the students used antibiotics without prescriptions with no statistical differences by age, sex, residence, or type of universities. More than half of the students (51.7%) do not know the effect of antibiotics abuse on microbial resistance. Most self-treated antibiotics were used to manage gastroenteritis symptoms (70%), respiratory symptoms (63%), and dental infections (36%), other causes such as headache or prophylactic reasons (21%). About 91.7% of the self-medicated students reported access to antibiotics from the pharmacy without a prescription and 71% of them mentioned discontinuation of a course of antibiotics at least once during the last year. About 81% of the students who do not know the effect of antibiotic abuse are self-medicated versus 75% of their counterpart who know and this difference is statistically significant. The multivariate analysis identified the residence as an independent predictor of their knowledge (area of residence = 1.6, 95% confidence interval [1.1–2.3]). CONCLUSION: The prevalence of self-medication with antibiotics among university students in Cairo is high. Our findings highlight the urgent need for tailored interventions to control this practice.