A hydraulic stress simulator was employed to study the mechanical behavior of the calf pericardium used in the construction of cardiac valve leaflets. One hundred eighty pairs of tissue samples were subjected to tensile testing to rupture. One of the two samples from each of 144 pairs (four series of 36 pairs each) was sutured with commercially available threads made of nylon, silk, Prolene or Gore-Tex, while the other sample in each of these pairs was left unsewn. The remaining 36 pairs were employed as controls in which neither of the two samples was subjected to suturing. The sutured tissue samples showed a significant decrease in tensile strength at rupture (range: 11.81 to 26.04 MPa) when compared with unsutured samples (range: 39.38 to 87.96 MPa; p < 0.01). The application of morphological and mechanical selection criteria to maximize the homogeneity of the samples provided excellent fit with respect to the stress/strain curves. This method made it possible to carry out a predictive study of the mechanical behavior of a sutured sample, based on that observed in the corresponding unsutured fragment. The interaction of the different suture materials with the pericardial tissue was also assessed by comparing the mechanical behavior of the sutured samples with that of the control samples. At stresses of less than 0.8 MPa, samples sewn with Gore-Tex were found to show the least difference with respect to the controls, indicating that this material presented the lowest degree of interaction with the pericardium. In conclusion, the degree of the loss of resistance to tearing of the sutured samples is of no value in the selection of the optimal suture material. The selection process applied makes it possible to predict the mechanical behavior in response to suturing of a given unsewn tissue specimen by determining that of its sutured mate. The similarity between the findings in samples sewn with Gore-Tex and in the unsutured controls indicates a lesser degree of interaction between the suture material and the pericardium employed in the construction of cardiac valve leaflets.