Zwitterionic materials have gained considerable attention in biomedical applications due to their exceptional non-fouling and biocompatible properties. However, only a limited number of zwitterionic materials have been investigated and compared regarding in vivo implantation. In this study, we synthesized various zwitterionic materials, including poly (carboxy betaine acrylamide) (PCBAA), poly (trimethylamine N-oxide) (PTMAO), poly (carboxy betaine methacrylate) (PCBMA), and poly (sulfobetaine methacrylate) (PSBMA), to investigate the differences and dynamic changes in the foreign body reaction among these materials. In vitro experiments demonstrated that all four types of zwitterionic hydrogels exhibited extremely low protein adsorption and cell adhesion. However, significant differences were observed in vivo. Histological analysis revealed that both PCBMA and PSBMA exhibited resistance to capsule formation for three months, which is correlated to the gene expression data generated by qRT-PCR. Additionally, both PCBMA and PSBMA promoted angiogenesis in the surrounding tissues. Conversely, PCBAA and PTMAO did not exhibit apparent anti-fibrosis ability or angiogenesis, possibly due to the degradation of acylamido groups in PCBAA and PTMAO side chains within animal bodies. The findings of this study provide insights into the performance and dynamics of various zwitterionic materials regarding the foreign body reaction, thus aiding the selection and design of zwitterionic materials for use in implantable biomaterials and biomedical devices.