The thermal properties and crystallization of biodegradable and optically active poly[(S)-2-hydroxybutyrate] [P(S-2HB)], poly(l-lactide) (PLLA), poly(d-lactide) (PDLA) and their blends were investigated. The results of differential scanning calorimetry, wide-angle X-ray scattering (WAXS), and polarized optical microscopy first indicated heterostereocomplexation between biodegradable and optically active polyesters having different chemical structures and opposite configurations, that is, P(S-2HB) and PDLA. The melting temperature of the heterostereocomplex was higher than those of pure polymers. Such cocrystallization was not observed for P(S-2HB)/PLLA blends having identical configurations. The WAXS profile of P(S-2HB)/PDLA heterostereocomplex was very similar to those of the PLLA/PDLA and P(S-2HB)/P(R-2HB) homostereocomplexes and each crystalline diffraction peak of the heterostereocomplex was located between those of the homostereocomplexes. The present study strongly suggests that heterostereocomplexation will provide a novel versatile method for preparing biodegradable polyester materials with a wide range of physical properties and biodegradability.