The importance of the microstructure on the permeability of silicone hydrogels is widely appreciated but is poorly understood and minimally investigated. In contrast with most conventional hydrogels, the water content and water structuring within silicone hydrogels cannot be solely used to predict their permeability. To ensure comfort and eye health, these materials must simultaneously exhibit both high oxygen permeability and high water permeability. The materials achieve these opposing requirements based on a composite of nanoscale domains of oxygen-permeable (silicone) and water-permeable hydrophilic components. This study correlated the ion permeation coefficients of a selection of commercially available silicone hydrogel contact lenses with their morphological structure and chemical composition. Donor/receiver conductivity measurements were recorded using a dual-chamber diffusion system, which allowed permeability profiles and coefficients to be calculated. Differential scanning calorimetry was used to measure water structuring properties through subdivision of the freezing water component into polymer-associated water (loosely bound to the polymer matrix) and ice-like water (unimpeded with a melting point close to that of pure water). Small-angle x-ray scattering, and environmental scanning electron microscopy techniques were used to investigate the structural morphology of the material over a range of length scales. Significant, and previously unrecognised, differences in morphology between individual materials at nanometre length scales were determined. These exploratory techniques facilitate the understanding of the effects of the bulk morphology on the permeability behaviour of each silicone material; this will aid the design and performance of the next generation of ocular biomaterials, capable of maintaining enhanced ocular homeostasis.