Lipase-based catalysts were tested for the ring-opening polymerization of D-, L- and D,L-lactide isomers, highlighting the different specificity of the enzyme toward these isomers. Free form of Candida antarctica lipase B (CALB) and its clay- and acrylic resin- immobilized forms were compared. For L- and D,L-lactide monomers only short oligomers were obtained. The acrylic resin immobilized form of CALB (NOV0-435) led to a complete conversion of D-lactide to PDLA with a M-n of 2600 g/mol, whereas the clay-immobilized and free forms of CALB exhibited slower kinetics and produced chains of lower M-n. Copolymerization reactions between epsilon-caprolactone and lactide isomers were performed using NOV0-435 as bio-catalyst. Random copolyesters were successfully synthesized by copolymerizing D-lactide with epsilon-caprolactone. Better results were obtained with a two-step reaction, starting from presynthesized polycaprolactone chains, compared with the one-pot copolymerization. Conducting this two-step copolymerization in the presence of organo-modified montmorillonite allowed the successful synthesis of copolymer/clay nanohybrids. (C) 2015 Elsevier B.V. All rights reserved.