Although widely used in the treatment of common cancers, paclitaxel causes angialgia/phlebitis in 60–70% of patients when administered intravenously to the upper extremities. However, useful laboratory models for the study of angialgia and phlebitis are currently lacking. The purpose of this study was to establish a new application of the real-time cell-monitoring analysis (RTCA) system to detect responses of human umbilical vein endothelial cells (HUVECs) to paclitaxel. We examined the possibility of applying this method to detect the risk of developing angialgia/phlebitis as a side effect of anticancer reagents. HUVECs were seeded onto an E-plate. After 24 h of culture, paclitaxel and carboplatin were added to each well and changes in electrical impedance were then recorded for 72 h. Electrical impedance, outputted as cell index (CI) values, enabled the time-dependent monitoring of the effects of chemotherapeutics on HUVEC viability. Paclitaxel caused a greater concentration- and time-dependent decrease in HUVEC CI values than with carboplatin. These findings agree with clinical case data showing that taxanes cause angialgia/phlebitis more frequently than platinum therapies. Furthermore, CI values correlated with increased levels of the inflammatory markers intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and phospho-nuclear factor (P-NF)-κB. Together, these data suggest that our RTCA-based experimental method provides a useful in vitro model for the study of chemotherapy-induced angialgia/phlebitis.