Ethnopharmacological relevance A rhizome of Phragmites communis Trinius has been used in traditional medicine to remove a heat, relieve vomiting and fever, nourish body fluids, and treat diseases like cancers. However, the safety of Phragmitis rhizoma has not yet been fully assessed. Aim of the study: The present study evaluated the genotoxicity of an aqueous extract of Phragmitis rhizoma (AEPR). Materials and methods The genotoxic potential of AEPR was evaluated using both in vitro and in vivo assay systems: a bacterial reverse mutation (AMES) test using auxotrophic mutant strains of Salmonella typhimurium (TA100, TA1535, TA98, TA1537) and Escherichia coli (WP2 uvrA), a chromosomal aberration test using Chinese hamster lung cells, and a micronucleus test using bone marrow cells from male ICR mice subjected to an oral administration of AEPR. All tests were completed in compliance with the OECD guidelines or regional regulatory standards for toxicity study, and Good Laboratory Practice. Results When compared with the negative control, no genotoxic signs related to the AEPR treatment were observed in the AMES test up to 5000 μg/plate of AEPR and in the chromosomal aberration test up to 500 μg/ml of AEPR regardless of metabolic activation. Repeated oral administration of AEPR up to 5000 mg/kg/day for 2 days did not affect the body weight gains or mortalities of the experimental mice and did not induce any significant changes in the frequency of micronucleated polychromatic erythrocytes. Conclusions The present study demonstrated that aqueous extract of Phragmitis rhizoma is safe regarding genotoxicity in an experimental model at least under the conditions tested. Further toxicity assessment in a human clinical study should be done to support the safe use of Phragmitis rhizoma by patients and healthcare providers.