Polyester blending of poly(-caprolactone) (PCL) with poly(D,L-lactide) (PLA) and their random copolymers (R CL/LA ) was found to be a convenient approach to regulate the degradation and drug release behaviors of the polyesters. The blend composition and compatibility both affected its degradation and drug release behavior. A DSC study showed that PCL was compatible with 50:50 poly(CL-CO-D,L-LA) (R 50/50 ) but incompatible with 25:75 poly(CL-CO-LA) (R 25/75 ) and PLA homopolymer. The hydrolysis experiments indicated that with the same CL/LA segment proportion, compatible blends (PCL/R 50/50 ) had higher water content and faster weight loss than incompatible blends (PCL/ PLA, PCL/R 25/75 ). In the compatible blends the PCL degradation rate was increased while that of R 50/50 was decreased. The controlled release kinetics, diffusion constants, and permeation coefficients of the polymer blends were measured by using northindrone (NTD) as a model. The NTD release rates from the polyester blends increased as the CL unit fraction increased but decreased with increasing the LA unit fraction in the blends. With the same CL/LA unit ratios, the NTD release rate from the compatible blend was slower than that from the incompatible blend. The NTD release from the polyester blend was controlled by the diffusion process in the early stage, but the degradation-caused NTD release was later involved. By tailoring the blend composition to such an extent that the degradation-caused release compensated the decline of the diffusion-caused release, a zero-order NTD release was achieved.