Realistic mathematical modeling can greatly facilitate the optimum design of matrix-controlled release (MCR) devices. Here, we present a practical example of a relevant methodology, based on a previously developed model for symmetrical, three-layer MCR devices. The experimental system is based on PDMS matrices incorporating 10% of poly(ethylene glycol) and loaded with theophylline. The matrices were either single-layer devices uniformly loaded with theophylline or symmetrical three-layer devices with a uniformly loaded inner layer and theophylline-free outer layers. The theophylline loads, and the geometrical characteristics of the multilayer matrices, were chosen according to general guidelines for improved uniformity of rate, previously formulated by model calculations. As anticipated, these devices were found to effectively stabilize the rate of release, as compared to the corresponding single-layer system. The main kinetic characteristics of the experimental systems were then successfully reproduced theoretically by a set of input parameters (pertaining to the transport properties of the polymer solute solvent system), derived mainly from the release experiments in monolithic matrices. Finally, the same input parameters were used for exploring theoretically the range of the three-layer device parameters that are expected to preserve the observed improved performance of the experimental systems.