In this study, the ability to control the shell thickness of hollow polymeric microspheres prepared using electrohydrodynamic processing at ambient temperature was investigated. Polymethylsilsesquioxane (PMSQ) was used as a model material for the microsphere shell encapsulating a core of liquid perfluorohexane (PFH). The microspheres were characterized by Fourier transform infrared spectroscopy and optical and electron microscopy, and the effects of the processing parameters (flow-rate ratio, polymer concentration and applied voltage) on the mean microsphere diameter (D) and shell thickness (t) were determined. It was found that the mean diameters of the hollow microspheres could be controlled in the range from 310 to 1000 nm while the corresponding mean shell thickness varied from 40 to 95 nm. The results indicate that the ratio D : t varied with polymer concentration, with the largest value of approximately 10 achieved with a solution containing 18 wt% of the polymer, while the smallest value (6.6) was obtained at 36 wt%. For polymer concentrations above 63 wt%, hollow microspheres could not be generated, but instead PMSQ fibres encapsulating PFH liquid were obtained.