Abstract: OBJECTIVE To provide reference for clinical safe drug use by mining and analyzing the risk signals of adverse events of three Bruton’s tyrosine kinase(BKT) inhibitors, ibrutinib, acalabrutinib and zanubrutinib. METHODS Based on the Public Data Open Project of the US Food and Drug Administration(OpenFDA), adverse event reporting data for three BTK inhibitors from January 1, 2004 to September 30, 2021 were retrieved. RESULTS According to the FDA, 49 006, 2 056 and 246 adverse events had been reported in relation to ibrutinib, acalabrutinib, and zanubrutinib, respectively. Using the proportional imbalance method for detection, there were a total of 769 adverse event signals with statistical significance, which were mainly focused on infection, blood and lymphatic system, heart diseases, skin and subcutaneous tissue, vascular and lymphatic vessel vessels, etc. In addition, new adverse events were observed, such as sepsis, pulmonary hemorrhage, nail disorder, brittle nails, taste disorder, etc. Compared to acalabrutinib and zanubrutinib, ibrutinib had the most adverse event risk signals, and the correlations of adverse event risk signals among them were diverse. CONCLUSION By conducting a multi-dimensional mining analysis of the three BTK inhibitors using the OpenFDA database, the study prompts clinical physicians to be alert to the risk of adverse drug events during clinical use, timely diagnose and treat corresponding symptoms, so as to promote rational drug use.