In this study we prepared hydrogels based on 2-hydroxyethyl methacrylate (HEMA): PHEMA homopolymer and two terpolymers of HEMA, itaconic acid (IA) and two poly(alkylene glycol) (meth) acrylates (PAGM): poly(ethylene glycol)6 acrylate (P(HEMA/IA/PAGM1)) and poly(propylene glycol)5 methacrylate (P(HEMA/IA/PAGM2)). Hydrogels were synthesized by gamma-irradiated radical polymerization and subjected to swelling measurements and genotoxicity evaluation. Swelling studies confirmed that these hydrogels deserve consideration as biomaterials due to their ability to swell in phosphate buffer but maintaining physical integrity for a prolonged contact time after equilibrium state has been reached. Comet assay showed certain genotoxic effect following cell exposure to extracts of hydrogels, which was dependent on the concentration of extracts, chemical composition of hydrogels and the degree of crosslinking. The influence of concentration on genotoxicity was the most pronounced. The synthesis of these novel HEMA-based hydrogels should be optimized so as to reduce their toxicity and enable the use in clinical practice.