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Brucellosis is a contagious and febrile disease endemic to Iran. Increased antibiotic resistance in endemic areas may lead to increased risk of treatment failure and the risk of disease relapse. This systematic review and meta-analysis was performed to determine the antibiotic susceptibility profiles of Brucella species isolated from clinical and environmental samples in Iran.Using national and international databases and extracted keywords from the MeSH database, a fully computerized search was done until 11 June 2018. Of 385 collected studies on the prevalence of drug resistance of Brucella species isolated in Iran, six articles were included in the meta-analysis using predefined eligibility criteria.Overall resistance rates of Brucella species to different antibiotics in Iran were as follows: doxycycline: 0%, tigecycline: 5.1%, trimethoprim/sulfamethoxazole: 5.7%, ciprofloxacin: 2.7%, streptomycin: 5%, rifampin: 9.5%, tetracycline: 4.6%, gentamicin: 3.9%, moxifloxacin: 0%, erythromycin: 33.3%, azithromycin: 5.8% and ceftriaxone: 6.3%.Our study revealed that the prevalence of drug resistance of Brucella species isolated from clinical and environmental samples in Iran was acceptable and low. However, care should be exercised in the use of common antibiotics for the treatment of brucellosis to prevent the spread of drug resistance.