A theoretical and experimental approach is proposed for the investigation of mismatched worm gear drives. The major objectives of the project include: (1) computer-aided simulation of the performance and behaviors of worm gears under real working conditions including manufacturing errors and elastic deformation due to the external load; (2) based on the simulation results, the development of an advanced approach for tooth strength evaluation, tooth mesh analysis, prediction of transmission error, and optimization of design parameters; and (3) experimental investigation to verify the theoretical analysis results and the CAD simulation. In order to achieve the objectives, several advanced techniques are applied, including elastic gearing theory, virtual manufacture, 3-D CAD simulation, artificial neural networks, genetic algorithms and advanced experimental methods. The research is mainly focused on mismatched involute cylindrical worm gears, but the principles are also applicable for other types of worm gears.