This article presents a high-voltage (HV) pulse driver based on silicon-on-insulator (SOI) technology for biomedical ultrasound actuators and multi-channel portable imaging systems specifically. The pulse driver, which receives an external low-voltage drive signal and produces high-voltage pulses with a balanced rising and falling edge, is designed by synthesizing high-speed, capacitor-coupled level-shifters with a high-voltage H-bridge output stage. In addition, an on-chip floating power supply has also been developed to simplify powering the entire system and reduce static power consumption. The electrical and acoustic performance of the integrated eight-channel pulse driver has been verified by using medical-grade ultrasound probes to acquire the transmit/echo signals. The driver can produce pulse signals >100 Vpp with rise and fall times within 18.6 and 18.5 ns, respectively. The static power required to support the overall system is less than 3.6 mW, and the power consumption of the system during excitation is less than 50 mW per channel. The second harmonic distortion of the output pulse signal is as low as −40 dBc, indicating that the integrated multi-channel pulse driver can be used in advanced portable ultrasonic imaging systems.