This article presents an application-specific integrated circuit (ASIC) designed for intra-vascular ultrasound imaging that interfaces 64 piezoelectric transducer elements to an imaging system using a single micro-coaxial cable. Thus, it allows a single-element transducer to be replaced by a transducer array to enable 3-D imaging. The 1.5-mm-diameter ASIC is intended to be mounted at the tip of a catheter, directly integrated with a 2-D array of piezoelectric transducer elements. For each of these elements, the ASIC contains a high-voltage (HV) switch, allowing the elements to transmit an acoustic wave in response to an HV pulse generated by the imaging system. A low-noise amplifier then amplifies the resulting echo signals and relays them as a signal current to the imaging system, while the same cable provides a 3-V supply. Element selection and other settings can be programmed by modulating configuration data on the supply, thus enabling full synthetic aperture imaging. An integrated element test mode measures the element capacitance to detect bad connections to the transducer elements. The ASIC has been fabricated in a 0.18- $\mu \text{m}$ HV CMOS technology and consumes only 6 mW in receive. Electrical measurements show correct switching of 30-V transmit pulses and a receive amplification with a 71-dB dynamic range, including 12 dB of programmable gain over a 3-dB bandwidth of 21 MHz. The functionality of the ASIC has been successfully demonstrated in a 3-D imaging experiment.