The number of cancer survivors is increasing because of recent advances in cancer treatments. Molecular target drugs, such as vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have demonstrated the encouraging efficacy. However, anti-cancer drugs are known to frequently induce severe, sometimes life-threatening cardiotoxicity, such as arrhythmias and contractile dysfunction. The assessment of drug-induced proarrhythmic risk using human iPS cell-derived cardiomyocytes (hiPSC-CMs) has been validated internationally, while it has not been established to predict the cardiac contractile dysfunction. Here, we investigated the effect of VEGFR-TKIs on contractile changes of hiPSC-CM sheets (iCell cardiomyocytes 2.0, Fujifilm Cellular Dynamics International) using an image-based motion vector system (SI8000, Sony). Chronic treatment with sorafenib or pazopanib significantly decreased in the contraction and relaxation velocity of hiPSC-CMs, whereas nintedanib did not. We also found that these in vitro results were correlated with the FDA Adverse Event Reporting System (FARES) analysis. Taken together, the motion analysis of hiPSC-CMs is a valuable approach for assessing drug-induced cardiac contractile dysfunction.