A one-step extrusion process under physiological conditions yielded calcium alginate-poly-(ethylene glycol) hybrid microspheres (Alg-PEG-M), for which the physical properties were adjustable by the macromolecular characteristics of the components, their concentration as well as the process conditions. A solution containing a mixture of sodium alginate (Naalg) and multiarm vinyl sulfone-terminated PEG(PEG-VS) was extruded into a receiving bath providing calcium ions and a thiol cross-linker. Covalent cross-linking of PEG-VS occurred in the rapidly gelled spherical calcium alginate (Caalg) matrix. After liquefaction of the Caalg, the cross-linked PEG remained spherical. The stoichiometric ratio thiol/VS was decisive for the PEG gel stability. The permeability of the hydrogels could be tuned by adequate choice of the arm length of PEG-VS, while the swelling behavior was influenced by its concentration, the quality of the storage solvent, and the presence or absence of the Caalg matrix. Only slight differences of the mechanical resistance were observed after the dissolution of Caalg.