Polyesters with cyclic structures in the main chain typically possess superior mechanical and thermal properties together with chemical recyclability. Ring-opening polymerization (ROP) of bridged or fused bicyclic lactones is a simple, and in most cases controlled method to synthesize polyesters with alicyclic moieties in the polymer backbone. The stereochemistry of the alicyclic structures has a great effect on the polymer properties, which can be regulated by varying the polymerization conditions. Here, we report a systematic investigation on the ROP of 2-oxabicyclo[2.2.2]octan-3-one ([2.2.2]VL) under different conditions. When initiated by n-butyl lithium (n-BuLi) or catalyzed by trifluoromethanesulfonic acid (TfOH) in the presence of benzyl alcohol, P[2.2.2]VLs containing all cis-1,4 disubstituted cyclohexane ring were obtained. However, P[2.2.2]VLs initiated by sodium methoxide (MeONa) or catalyzed by organic superbase contained both cis and trans isomeric structural units. The cis to trans transformation mechanism under these conditions was manifested, and the effect of stereochemical variations on the properties of P[2.2.2]VL was revealed. The stereoregular P[2.2.2]VLs, both cis and trans, exhibited higher crystallinity and melting temperatures (T_m) than those of the stereoirregular isomers. Finally, the degradation of P[2.2.2]VL with acid at high temperature could recover 3-cyclohexenecarboxylic acid.