In this study, a salt-leaching using powder (SLUP) scaffold with penetrated macropores was proposed to enhance cell proliferation. A SLUP scaffold is a salt-leaching scaffold with an arbitrary pore configuration. Although SLUP scaffolds have several advantage over traditional salt-leaching scaffolds, the cell ingrowth might be poor compared with solid freeform fabrication scaffolds, which have well-interconnected pores. We therefore proposed SLUP scaffolds with penetrated macropores to assist the cell ingrowth. First, polycaprolactone (PCL) powders with a grain size of 63–100 μm and NaCl powders with a grain size of 100–180 μm were prepared. Next, a uniformly perforated mold was fabricated using an rapid prototyping (RP) system. Then, 500-, 820-, or 1200-μm-diameter needles were inserted into the holes of the RP mold. Subsequently, the mold was filled with a mixed powder of PCL/NaCl (30 : 70 vol %). The mold was then heated in the oven at 100°C for 30 min, and both the needles and the mold were removed from the PCL/NaCl mixture. Then, the PCL/NaCl mixture was soaked in DI water for 24 h to leach out NaCl particles and dried in a vacuum desiccator for 24 h. The porosity of fabricated scaffolds was calculated using a simple equation, and the compressive stiffness was measured using a universal testing machine. Moreover, each scaffold (10 × 10 × 10 mm3) was seeded with 100,000 Saos-2 cells and cultured for 14 days. The cell proliferation characteristics were assessed using a CCK-8 assay at 1, 7, and 14 days for comparison with the control scaffolds, that is, the SLUP scaffolds with no penetrated macropores. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40240.