Electrostatic discharge (ESD) failures in high-speed integrated circuits (ICs) cause critical reliability problems in electronic devices. Transient voltage suppressor (TVS) diodes are installed on high-speed I/O traces to improve system-level ESD protection. To protect the circuit, the majority of ESD current must flow into the external TVS diode rather than into the IC, but due to turn-on behavior, the TVS diode may not snap back when needed and the IC's internal protection may take most of the current. These race conditions between the internal and external ESD protection circuits were investigated for a universal serial bus(USB) interface board. The transient turn-on behavior of the on-chip and off-chip protection circuitry was characterized by measurements and by system efficient ESD design (SEED) simulations. The effect of transmission line pulses (TLP pulses) and power supply voltages of different sizes on the response of the protection circuitry were monitored and compared with SEED simulations. SEED models showed good agreement with measurements and were used to study the impact of passive components added to a high-speed trace or within the IC package on the ESD protection response. Results show the importance of properly accounting for the parasitic resistance and inductance between the on-chip diode and off-chip TVS diode, as well as the length of the transmission line when choosing the external TVS device. Results also show that testing must be performed using mid-level events to account for possible problems due to race conditions.