Edge-lit light guide panels (LGPs) with micropatterned surfaces represent a new technology for developing small- and medium-sized illumination sources for application such as automotive, residential lighting, and advertising displays. The shape, density, and spatial distribution of the micro-optical structures (MOSs) imprinted on the transparent LGP must be selected to achieve high brightness and uniform luminance over the active surface. We examine how round-tip cylindrical MOSs fabricated by precision micromilling can be used to create patterned surfaces on low-cost transparent polymethyl-methacrylate substrates for high-intensity illumination applications. The impact of varying the number, pitch, spatial distribution, and depth of the optical microstructures on lighting performance is initially investigated using LightTools™ simulation software. To illustrate the microfabrication process, several LGP prototypes are constructed and tested. The prototypes include an “optimized” array of MOSs that exhibit near-uniform illumination (approximately 89%) across its active light-emitting surface. Although the average illumination was 7.3% less than the value predicted from numerical simulation, it demonstrates how LGPs can be created using micromilling operations. Customized MOS arrays with a bright rectangular pattern near the center of the panel and a sequence of MOSs that illuminate a predefined logo are also presented.