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The Rankine microturbine is a microelectromechanical system being developed for generating mechanical and electrical power from waste heat, such as from automobile exhaust gases. The design of this device faces the difficult challenges of creating structures rotating at high-speeds (1 000 000 r/min), sustaining large internal pressures (3 MPa) and temperature gradients (100°C/mm), and machining millimeter-sized components of ceramic or metallic materials with micrometer tolerances. Here, we report an integrated approach to guide the design of the Rankine microturbine by analyzing its performance and reliability. The primary performance metrics and design challenges were identified, and a modeling approach based on a combination of low-order analytical models and finite-element calculations was developed for thermal and structural analyses. The results of these models, along with their implications for the selection of size, shape, and materials, are presented. The need for materials with low thermal conductivity (10 W/m/K) for the rotor and sidewalls is highlighted, along with the expected levels of stresses and deformation and their impact on reliability. Viable device configurations and materials (silica, zirconia, and titanium alloys) are proposed for operation at elevated temperatures. The approach to the modeling used in this paper is expected to be of value for the preliminary design of other microsystems subjected to stringent mechanical and thermal loading.