The study was carried out to estimate the prevalence of self-medication with antibiotics among tertiary level students in Accra (Ghana) and evaluate factors associated with the practice. This was a descriptive cross-sectional study and involved face-to-face interviews of 600 respondents selected by convenient sampling. Prevalence of self medication was 70% (95% CI: 66.3-73.7), and the practice was significantly lower among medically inclined students (OR: 0.2, 95% CI: 0.1-0.4, p < 0.001). Among the respondents who practiced self medication, the most common frequency of antibiotic usage was at intervals of one month (30%, 95% CI: 25.6-34.4%), and the most common antibiotic used was amoxacillin (23.9%, 95% CI: 21.0-26.8%). Treatment failure were reported by 35% (95% CI: 30.5-39.6%) of the respondents, and the main reasons cited for self medication were that, it was less expensive compared to medical care in the hospital and secondly, medical care in hospitals were associated with long delays. Forty nine percent (95% CI: 44.2-53.8%) of the respondents had poor knowledge about the health implications of irrational use of antibiotics, and 46% (95% CI: 41.2-50.8%) did not comply with the completion of the full course of antibiotics. Self medication among tertiary students in Accra is an important public health problem and this may reflect the situation among tertiary students in the whole of Ghana.