Ring-opening copolymerization of L-lactide (LLA) and 1,3-trimethylene carbonate (TMC) blends with LLA/TMC feed ratios from 90/10 to 50/50 was realized at 110 °C or at 180 °C for various time periods, using low toxic zirconium (IV) acetylacetonate (Zr(Acac)4) as initiator. The resulting copolymers exhibit different chain microstructures. Copolymers obtained at 110°C exhibit a gradient chain structure with the presence of lactidyl sequences next to very short ones, and are semi-crystalline. In contrast, copolymers obtained at 180°C are amorphous because of a more random chain microstructure with the presence of larger amounts of medium sequences. Degradation of the copolymers were carried out in pH 7.4 phosphate buffer at 37 °C. Analytical techniques such as 1H-NMR, DSC, GPC and XRD were used to monitor the degradation. Initially amorphous copolymers can remain amorphous during degradation because of the highly random units distribution, and equivalent LLA and TMC contents. However, initially amorphous copolymers containing larger amounts of lactidyl units are able to crystallize during degradation because of the presence of relatively long LLA blocks. Insofar as initially semi-crystalline copolymers are concerned, degradation occurs preferentially in the amorphous zones. Therefore, various degradation behaviors and degradation rates can be obtained by varying the chemical composition, chain microstructure and morphology of PLLA-PTMC copolymers.