This article deals with the mechanical interpretation of the in-situ diagonal compression test on masonry panels, through a non-linear numerical modeling, and proposes a methodology for the evaluation of the tensile strength and the shear modulus of masonry. The results of a wide experimental campaign on 24 masonry panels in the region of Tuscany (Italy) are presented; the obtained material parameters are classified according to the masonry typology. A critical review of the frequently used methodologies for the interpretation of the diagonal compression test, regulated by ASTM and RILEM (ASTM E 519-02, 2002; RILEM TC-76 LUM, 1994), has been made, showing the inaccuracy and incompleteness of both. The aims of this research are to simulate the behavior of different masonry typologies and to give a numerical interpretation of the tests, in order to determine the tensile strength of the panel. This parameter is very important for the seismic safety check of masonry panels in existing buildings, according to many seismic codes.