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Introduction: Antibiotic self-medication is a global public health concern contributing to antibiotic resistance. This systematic review and meta-analysis aim to assess the prevalence of antibiotic self-medication and its associated factors in Ethiopia., Methods: A comprehensive search of electronic databases was conducted from MEDLINE (PubMed), Scopus, Google Scholar and Web of Science to identify relevant studies published between 2000 and 2024. Adult households, undergraduate university students and health care professionals who had taken antibiotics without a prescription in the household setting were included in this review. The primary outcome of this review is antibiotic self- medication. The random-effects model was used to estimate pooled prevalence rates. The outcome measure was analyzed with STATA version 17 software., Results: A total of nine studies were included in the Meta-analysis, comprising a sample size of 5908 participants. The pooled prevalence of antibiotic self-medication among Ethiopians was found to be 46.14 with 95% Confidence Interval [35.71, 56.57]. The most frequently used classes of self-medicated antibiotics were penicillins, followed by tetracyclines. Community pharmacies were the source of information that individuals utilized. The most common reported reasons for antibiotic self-medication include previous experience of treating a similar illness, to save cost, lack of time and avoiding waiting time for medical services. Participants having less than high school educational level was the most commonly reported factor associated with self-medication antibiotics., Conclusion: Antibiotic self-medication is a prevalent practice in Ethiopia. This underscores the need for targeted interventions such as educating people about the risks associated with using antibiotics without medical guidance, which results in a reduction in antibiotic resistance., (© 2024. The Author(s).)