Skin-interfaced wearable systems with integrated microfluidic structures and sensing capabilities offer powerful platforms for monitoring the signals arising from natural physiological processes. This paper introduces a set of strategies, processing approaches, and microfluidic designs that harness recent advances in additive manufacturing [three-dimensional (3D) printing] to establish a unique class of epidermal microfluidic (“epifluidic”) devices. A 3D printed epifluidic platform, called a “sweatainer,” demonstrates the potential of a true 3D design space for microfluidics through the fabrication of fluidic components with previously inaccessible complex architectures. These concepts support integration of colorimetric assays to facilitate in situ biomarker analysis operating in a mode analogous to traditional epifluidic systems. The sweatainer system enables a new mode of sweat collection, termed multidraw, which facilitates the collection of multiple, independent sweat samples for either on-body or external analysis. Field studies of the sweatainer system demonstrate the practical potential of these concepts.