Digital microfluidics (DMF) is a promising technique for carrying out miniaturized, automated biochemical assays in which discrete droplets of reagents are actuated on the surface of an array of electrodes. A limitation for DMF is nonspecific protein adsorption to device surfaces, which interferes with assay fidelity and can cause droplets to become unmovable. Here, we report the results of a quantitative analysis of protein adsorption on DMF devices by means of confocal microscopy and secondary ion mass spectrometry. This study led us to a simple and effective method for limiting the extent of protein adsorption: the use of low concentrations of Pluronic F127 as a solution additive. This strategy has a transformative effect on digital microfluidics, facilitating the actuation of droplets containing greater than 1000-fold higher protein concentrations than is possible without the additive. To illustrate the benefits of this new method, we implemented a DMF-driven protein digest assay using large concentrations (1 mg/mL) of protein-substrate. The use of Pluronic additives solves a sticky problem in DMF, which greatly expands the range of applications that are compatible with this promising technology.