Short diffusion paths and high specific interfacial areas in microstructured devices can increase mass transfer rates and thus accelerate multiphase reactions. This effect can be intensified by the application of ultrasound. Herein, we report on the design and testing of a novel versatile setup for a continuous ultrasound-supported multiphase process in microstructured devices on a preparative scale. The ultrasonic energy is introduced indirectly into the microstructured device through pressurized water as transfer medium. First, we monitored the influence of ultrasound on the slug flow of a liquid/liquid two-phase system in a channel with a high-speed camera. To quantify the influence of ultrasound, the hydrolysis of p-nitrophenyl acetate was utilized as a model reaction. Microstructured devices with varying channel diameter, shape, and material were applied with and without ultrasonication at flow rates in the mL min−1 range. The continuous procedures were then compared and evaluated by performing a simplified life cycle assessment.