<p>As a traditional Chinese medicine (TCM) composed of As₂S₂, realgar has been widely used for treating various diseases. However, its safety has raised significant concerns due to the well-documented toxicity of arsenic. The Chinese Pharmacopoeia has imposed strict controls on the dosage of realgar, but the bioaccessibility and health risks associated with arsenic in realgar-containing TCMs remain poorly understood. This study developed a hydride generation–atomic fluorescence spectrometry (HG-AFS) method to determine the total arsenic and bioaccessible arsenic contents in 20 realgar-containing TCMs through wet digestion and simulated gastrointestinal fluid extraction. Health risk assessments were evaluated from the bioaccessible arsenic content using single pollution index (Pi), maximum daily intake (MDI), estimated daily intake (EDI), hazard quotient (HQ), and carcinogenic risk (CR). Additionally, the particle size of realgar in representative preparations was analyzed using a light microscope. The tested realgar-containing TCMs exhibited significant variations in the contents of total arsenic and bioaccessible arsenic. Bioaccessible arsenic is a more reasonable indicator for the safety evaluation of realgar-containing TCMs. The daily dosage of realgar in its-containing TCMs exceeded the limit standard prescribed in the Chinese Pharmacopoeia. The evaluation of the health risk index suggested that arsenic in realgar-containing TCMs exceeded the corresponding regulatory thresholds. Furthermore, realgar crystals in preparations were not uniform and exhibited noticeable differences under the microscope. The current quality standards in the Chinese Pharmacopoeia are insufficient to ensure the safety of realgar-containing TCMs, which urgently need to be revised. The study provided scientific evidence for the quality control and clinical safety application of realgar-containing TCMs.</p> Graphical Abstract <p></p>