Biodegradable polymers with high mechanical strength, flexibility and optical transparency, optimal degradation properties and biocompatibility are critical to the success of tissue engineered devices and drug delivery systems. In this work, microfluidic devices have been fabricated from elastomeric scaffolds with tunable degradation properties for applications in tissue engineering and regenerative medicine. Most biodegradable polymers suffer from short half life resulting from rapid and poorly controlled degradation upon implantation, exceedingly high stiffness, and limited compatibility with chemical functionalization. Here we report the first microfluidic devices constructed from a recently developed class of biodegradable elastomeric poly(ester amide)s, poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate)s (APS), showing a much longer and highly tunable in vivo degradation half-life comparing to many other commonly used biodegradable polymers. The device is molded in a similar approach to that reported previously for conventional biodegradable polymers, and the bonded microfluidic channels are shown to be capable of supporting physiologic levels of flow and pressure. The device has been tested for degradation rate and gas permeation properties in order to predict performance in the implantation environment. This device is high resolution and fully biodegradable; the fabrication process is fast, inexpensive, reproducible, and scalable, making it the approach ideal for both rapid prototyping and manufacturing of tissue engineering scaffolds and vasculature and tissue and organ replacements.