AbstractBiomaterial sterilization is a prerequisite prior to patient's use, especially for scaffold implantation or injection. Various sterilization processes are mandated by the Food and Drug Administration including high‐pressure steam sterilization. Although high‐pressure steam or autoclave sterilization eliminates pathogens, it often leads to irreversible damages on soft materials such as hydrogels. In the current study, the impact of autoclave sterilization on cryogels made from several naturally‐derived polymeric precursors (alginate, hyaluronic acid, and gelatin) is analyzed. Specifically, the impact of polymer concentration on the structural and physical properties of autoclaved cryogels such as mechanics, swelling ratio, pore interconnectivity, and shape‐memory features is studied. The results demonstrate that at a given optimal polymer concentration, unique for each biopolymer investigated, autoclave sterilization does not substantially alter the microarchitectural or physical characteristics of cryogels, including their syringe injectability signature. In summary, when formulated under optimized polymer concentrations, autoclavable cryogels hold great potential for several biomedical applications, as they can be easily translated into clinical practice to benefit public health.