An efficient approach to full-wave impedance extraction is developed that accounts for substrate effects through the use of two-layer media Green's functions in a mixed-potential-integral-equation (MPIE) solver. Particularly, the choice of implementation for the layered media Green's functions motivates the development of accelerated techniques for both volume and surface integrations in the solver. Solver accuracy is validated against measurements taken on fabricated devices; solver efficiency is demonstrated by its 9.8X reduction in cost in comparison to the traditional integration approach. Categories and Subject Descriptors: B.7.2 [Design Aids]: Placement and routing, Simulation, Verification. General Terms: Algorithms.