Knoop microhardness studies were carried out on urinary calculi and synthesized calcium oxalate monohydrate (COM) crystals. COM calculi showed a higher value of microhardness than the synthesized crystals. Calcium oxalate dihydrate (COD) and uric acid (UA) stones showed microhardness values close to that of COM. In the case of mixed stones, the stone with COM showed higher hardness value than the stone with COD component. The presence of calcium phosphate (hydroxyapatite, HAP) in the mixed stones did not contribute in anyway to the overall hardness of the stones. The variation of microhardness with the orientation of COM calculi showed a cyclic pattern indicating the presence of alternate layers of crystalline and matrix materials.