INTRODUCTION: Nilotinib, an anti-tumor tyrosine kinase inhibitor against BCR-ABL1, has been clinically reported to cause QT prolongation, but currently lacks evidence for a risk of torsade de pointes. Indeed, it is poorly understood why nilotinib rarely induces torsade de pointes. METHODS AND RESULTS: We adopted two-dimensional human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) sheets to examine effects of nilotinib on their electrophysiological and mechanical properties besides intracellular calcium (Ca CONCLUSION: Nilotinib could deteriorate relaxation ability and temporal electrical integrity of the heart through impairing Ca