Identification and prevention of drug-related problems have become the central role of patient-centered pharmacy practitioners. After the initiation of patient-oriented pharmacy service, many studies evaluating magnitude of drug-related problems at facility level in Ethiopia have been conducted, though the extent of the problem at a national level remains unknown. Hence, this systematic review and meta-analysis is undertaken with the aim of quantifying the prevalence of drug-related problems in Ethiopian public healthcare settings using Cipolle/Strand classification system. Electronic databases were searched including PubMed, EMBASE, Web of Science, MEDLINE and HINARI, Google Scholar and ResearchGate for both published and unpublished works. Data on study characteristics and outcomes were extracted using the format developed on Microsoft Excel. The primary measure was the pooled prevalence of drug-related problems. The meta-analysis was conducted using OpenMeta[Analyst].A total of 17 studies were included in this systematic review and meta-analysis. The pooled prevalence of drug-related problems of patients who experienced at least one drug-related problem during their therapy was found to be 69.4% (95% confidence interval: 61.5–77.4). The most frequently reported types of drug-related problems were “need for additional drug and “noncompliance,” together accounting for more than half of the drug-related problems. The most frequently reported factors associated with drug-related problems were patients’ age, polypharmacy, comorbidities and the number days of hospital stay.The prevalence of drug-related problems in Ethiopian public healthcare settings was found to be high. Inconsistent reporting of drug-related problems was observed across the studies. It is imperative to design and implement interventions aimed at reducing drug-related problems. Responsible stakeholders should adopt uniform drug-related problem classification approach to ensure uniform reporting of drug-related problems in Ethiopian healthcare settings