BackgroundDespite their significant contribution to reducing mortality and morbidity from infectious diseases, antibiotics face challenges due to their inappropriate use, one of which is self-medication. This study assessed the prevalence of|| self-medication with antibiotics among Eritrean college students and its associated factors.MethodsAn analytical cross-sectional study evaluated the prevalence of self-medication with antibiotics among students from five colleges from September 2019 to February 2020. Participants were selected through simple random sampling, and each participant completed a structured questionnaire covering socio-demographic characteristics, knowledge and attitudes toward antibiotics, and self-medication practices. Logistic regression analysis was employed to identify factors associated with self-medication with antibiotics.ResultsThe study distributed 380 questionnaires, with 375 returned, yielding a response rate of 98.68%. Findings revealed that 80.3% of participants were familiar with antibiotics. Additionally, 18.8% agreed with non-prescription antibiotic use for simple ailments. Of the 252 respondents who answered, 67.1% reported self-medication with antibiotics. Within the preceding six months, the prevalence of such self-medication was 34.3%. Factors associated with self-medication included college affiliation, with participants from the College of Science (COS) exhibiting lower odds (AOR = 0.38, 95% CI: 0.16–0.91, p = 0.03) compared to the College of Business and Social Sciences (CBSS) students. Those living in dormitories had 2.4 times higher odds (AOR = 2.42, 95% CI: 1.7–5.02, p = 0.017) to self-medicate compared to those living with family. Moreover, individuals unaware of antibiotic resistance had higher odds (AOR = 2.41, 95% CI: 1.24–4.7, p = 0.009) of self-medication. Attitude score was also significantly associated with self-medication (AOR = 0.88, 95% CI: 0.8–0.98, p = 0.027).ConclusionsThese results highlight the necessity for tailored educational programs to advocate for appropriate antibiotic utilization and mitigate the prevalent misuse of antibiotics among college students. Initiatives focused on increasing knowledge about the dangers linked with self-medication and advocating for conscientious antibiotic usage are essential in combating the escalating challenge of antibiotic resistance and safeguarding public health.