Surface-enhanced Raman scattering (SERS) is a versatile spectroscopic technique that suffers from reproducibility issues and usually requires complex substrate fabrication processes. In this article, we report the use of a simple mass production technology based on Blu-ray disc manufacturing technology to prepare large area SERS substrates (∼40 mm) with a high degree of homogeneity (±7% variation in Raman signal) and enhancement factor of ∼6 × 10. An industrial high throughput injection molding process was used to generate periodic microstructured polymer substrates coated with a thin Ag film. A short chemical etching step produces a highly dense layer of Ag nanoparticles at the polymer surface, which leads to a large and reproducible Raman signal. Finite difference time domain simulations and cathodoluminescence mapping experiments suggest that the sample microstructure is responsible for the generation of SERS active nanostructures around the microwells. Comparison with commercial SERS substrates demonstrates the validity of our method to prepare cost-efficient, reliable, and sensitive SERS substrates.