In this study, two biodegradable polyesters [i.e., polylactic acid (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)] with complementarity in terms of mechanical performance have been combined, and a series of blends with a broad range of compositions has been prepared by thermal compounding. The evolution of phase morphologies with the variation of compositions has been characterized by using Fourier transform infrared spectroscopic imaging together with scanning electron microscope analyses. Thermal, mechanical, and biodegradation properties of the PLA/PHBHHx blends were systematically investigated. Mechanical properties were further analyzed by using theoretical models and correlated with the results of the morphology/structure and compatibility of the blends. Results indicate that PLA/PHBHHx blends are immiscible but can be compatible to some extent at certain compositions (e.g., PLA/PHBHHx (w/w) = 80/20 and 20/80). The physical properties of the blend could be fine tuned by adjusting the blend composition. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.