This paper presents experimental and theoretical studies of the adhesion between the drug-eluting layer and a Parylene C primer layer in coatings present on a model drug-eluting stent. To quantify adhesion, Brazil nut sandwich specimens were prepared mimicking the layers of this coating. These samples were stressed to fracture, and the resulting initial cracks at the Parylene C/drug interface were used to measure the dependence of interfacial fracture energy of mode mixity. The mating fracture surfaces were then analyzed using scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDX). The interfacial energy release rates were obtained over a wide variety of mode mixities. Adhesion and fracture mechanics models were then used to estimate the mode mixity dependency of interfacial fracture toughness. Fracture toughness was found to be larger under higher mode mixity than that under lower mixity and the analytical model showed close agreement with experimental results.