Microencapsulation within hydrogel microspheres holds much promise for drug and cell delivery applications. Synthetic hydrogels have many advantages over more commonly used natural materials such as alginate, however their use has been limited due to a lack of appropriate methods for manufacturing these microspheres under conditions compatible with sensitive proteins or cells. This study investigated the effect of flow rate and voltage on size and uniformity of the hydrogel microspheres produced via submerged electrospray combined with UV photopolymerization. In addition, the mechanical properties and cell survival within microspheres was studied. A poly(vinyl alcohol) (PVA) macromer solution was sprayed in sunflower oil under flow rates between 1100?mu L/min and voltages 010?kV. The modes of spraying observed were similar to those previously reported for electrospraying in air. Spheres produced were smaller for lower flow rates and higher voltages and mean size could be tailored from 50 to 1,500?mu m. The microspheres exhibited a smooth, spherical morphology, did not aggregate and the compressive modulus of the spheres (350?kPa) was equivalent to bulk PVA (312?kPa). Finally, L929 fibroblasts were encapsulated within PVA microspheres and showed viability >90% after 24?h. This process shows great promise for the production of synthetic hydrogel microspheres, and specifically supports encapsulation of cells. Biotechnol. Bioeng. 2012; 109:15611570. (c) 2012 Wiley Periodicals, Inc.