Poly(L-lactic acid) (PLLA) scaffolds with pore diameters from several micrometers to similar to 300 mu m were fabricated by a specially elaborated thermally induced phase separation technique. Two different coarsening protocols, i.e., normal coarsening and multi-step coarsening were compared in consideration of phase separation and domain growth. A normal coarsening route produced scaffolds with pore size from several micrometers to 150 mu m depending on the coarsening time after phase separation, accompanying with the emergence of isolated pores at long time coarsening. Scaffolds with large pores with size up to similar to 300 mu m were fabricated by the two-step coarsening technique, e.g., the PLLA-solvent (dioxane/water) system was coarsened at a temperature after phase separation for a period, followed by coarsening at a lower temperature for another period. in parallel with formation of the large pores, the interconnectivity between pores was also improved, which was evidenced by scanning electron microscopy, gelatin solution pervasion, and collagen entrapment. The present technique provides the ability to produce scaffolds with high purity, controllable microstructures, and ease of modification, and hence can be widely used in tissue engineering field. (c) 2006 Wiley Periodicals, Inc.