Lipase-catalyzed ring-opening polymerizations of lactones with various ring sizes (6- to 13- and the 16-membered ring) employing Novozym 435 demonstrate fascinating differences in their polymerization rates. These differences cannot be related to variations in physical properties such as the dipole moment of the lactones only. For example, 10-decanolactone, 11-undecanolactone, and 12-dodecanolactone show dipole moments of around 1.9 D, but the initial rate constant of their Novozym 435-catalyzed polymerization was found to be 0.10, 0.38, and 4.91 h(-1), respectively. The Michaelis-Menten constants K-M and V-max were measured for all lactones, and this revealed that the K-M was more or less independent of the ring size, suggesting similar affinities of the lipase for all lactones, while no obvious trend could be discerned for Vmax. However, conformational strain and transannular interactions present in medium ring lactones (ring size 8-12) affect the reactivity of these lactones in lipase catalysis in a similar way as was previously described for the alkaline hydrolysis of lactones, rationalizing the low reactivity of the 10-12-membered rings and the high reactivity of the 8-membered ring. To our surprise, there is a large discrepancy in lipase-catalyzed ring-opening polymerizations compared to the alkaline hydrolysis reactions with respect to the relative reactivity of lactones possessing a cisoid conformation of the ester bond: while the ratio in rates between delta-valerolactone and 12-dodecanolactone in a alkaline hydrolysis is 9400, the ratio in rates using Novozym 435-catalyzed polymerization is only 3. In fact, in the latter case lactones possessing a cisoid conformation are less reactive than large ring lactones possessing a transoid conformation. This mechanistic study also furnished polyesters with an increasing number of methylenes in their repeat unit. The polyesters can be readily prepared in reasonable molecular weights (> 10 000 g/mol). Preliminary thermal characterization of the polyesters shows, as expected, that the melting temperature and the melting enthalpy increase with an increasing number of methylenes in the repeat unit.