We investigated biodegradation and biocompatibility of poly(organophosphazenes). We prepared poly(organophosphazenes) having different side chain groups. The blood compatibility of poly(organophosphazenes) containing fluorinated side groups, poly(bis[trifluoroethoxy]phosphazene) (PbFP) and poly([trifluoroethoxy][ethyl glycinate]phosphazene) (PFGP), without heparinization were evaluated in vitro. The deformation and aggregation of platelets adhered on PbFP and PFGP were not observed and they suppressed platelet activation. Additionally, PbFP and PFGP showed a higher degradation rate, despite their high hydrophobic nature. We found that the high mobility of water in PbFP and PFGP was one of the important factors facilitating their degradation. Their polymer structures were formed in a more open nature, indicating that water easily attacked the backbone of the phosphorus and nitrogen atoms in the poly(organophosphazene). On the other hand, the proliferation of HeLa cells cultured on poly(organophosphazene) was reduced compared with that on the control tissue culture polystyrene.