To investigate the effect of the stereoisomeric composition of lactides as comonomers on the thermal behavior of polylactide (PLA), a series of PLAs, including poly(L-co-D-lactides), poly(L-co-meso-lactides), and poly(L-co-D-co-meso-lactides), were synthesized by the random copolymerization of lactide stereoisomeric mixtures. The thermal behavior of the PLAs was investigated by differential scanning calorimetry in detail. The glass transition temperature (T-g), melting temperature (T-m), and melting enthalpy (Delta H-m) of poly(L-co-D-lactides) and poly(L-co-meso-lactides) increased with increasing stereochemical purity (SCP). At the same SCPs, T-g, T-m, and Delta H-m of poly(L-co-D-lactides) were slightly higher than those of poly(L-co-meso-lactides) because meso-lactide differed from d-lactide in terms of their contributions to the disorder degree of PLA molecular chains. The relationship of T-g or Tm with the stereoisomeric composition of lactides as comonomers was established for poly(L-co-D-co-meso-lactides) on the basis of the experimental data and used to design and prepare PLAs with different T-g and T-m values.