The microdomain structure of polyurethanes (PUR) determines their unique physical properties and makes polyurethanes attractive candidates for various tissue engineering applications. 3D scaffolds based on polyurethanes with different contents of hard segments were fabricated by a salt-leaching/polymer coagulation method. The process parameters were carefully considered, particularly the polymer solution concentration and characteristics of the polyurethane, which are the critical parameters for the control of porosity and pore size distribution. In this study, 3D polyurethane scaffolds were fabricated with interconnected pores and porosity from 64% to 80%. Pore size distribution was evaluated using quantitative image analysis and mercury intrusion porosimetry (MIP). The scaffolds fabricated from polyurethanes with 70 wt.% of hard-domain content were found to have the best compression properties.