The mechanical and functional properties of engineered blood vessels are determined largely by the characteristics of the scaffold matrix. In the present study, bovine collagen, rat collagen, bovine fibrin and a 1:1 bovine collagen-fibrin mixture were used to mold vascular constructs containing isolated smooth muscle cells. Mechanical property testing showed that each material had a characteristic stress-strain profile and failure mode. Examination of the linear modulus indicated that bovine collagen was the stiffest material (modulus of 191.4± 4.9 kPa), while pure bovine fibrin was the least stiff (27.9±1.6 kPa). The collagen-fibrin mixture had an intermediate modulus (153.4±7.0 kPa), while pure rat collagen (39.5±1.4 kPa) was markedly less stiff than bovine collagen. Ultimate tensile stress was highest for the collagen-fibrin mixture scaffolds (49.7±3.0 kPa). Bovine collagen alone (36.1±0.8 kPa) was stronger than rat tail collagen (3.9±0.1 kPa), and was also stronger than bovine fibrin alone (15.6±1.2 kPa). Constructs made with fibrin compacted to a greater degree than purely collagen-based constructs, leading to a denser matrix and increased stress values. These studies show that the properties of engineered blood vessels can be modulated by combining different naturally-derived matrix materials.