This study integrates 3D printing and finite element analysis (FEA) to investigate the effect of micro-architectural characteristics on the mechanical properties of porous scaffolds. The studied characteristics include the thickness of the scaffold walls and the number of domains at the cross-section. We use 3D printing to fabricate scaffolds of deliberately designed microstructures to enable strict architecture control of the scaffolds. The longitudinal compressive properties of different scaffolds are first analyzed through experimental testing. Then, FEA is conducted to investigate the mechanical properties and the deformation mechanisms of the scaffolds. We find that decreasing wall thickness leads to failure mechanism transition from wall compression failure to buckling instability. For scaffolds with different wall thicknesses, the failure mechanisms and the critical loads are evaluated using the theory of thin plate buckling. For the characteristic of the number of domains, both experimental and FEA results show increasing effective stiffness with increasing domains. Interestingly, we find that with the material properties extracted from a single wall scaffold, the computational models tend to overestimate the effective compression modulus of scaffolds with larger numbers of walls or domains than the experimental data. This observation indicates possible size-dependent material properties in 3D printed structs. Our study demonstrates that integrating experiments and computational modeling can provide fundamental insights into the mechanical properties and deformation mechanisms of micro-architectured scaffolds and unveil unique small-scale material behaviors.