In biological adhesion experiments, cells use surface receptors to attach to ligand-coated substrata, and forces, such as centrifugation or shear forces, are used to remove cells. Receptors bind with a high-affinity lock-and-key mechanism, and their bonds are weaker than covalent bonds. The magnitude of the force at which the cell relents is quoted as the strength of adhesion. However, the character or direction of the force, which depends on the adhesion assay, can affect the results of an adhesion assay, even if forces of precisely the same magnitude are applied in the different assays. We demonstrate this principle by simulating the detachment of receptor-coated hard spheres from ligand-coated surfaces using normal, tangential, and shear forces after the particles are allowed to bind to steady state. For a single bond, a 20-fold greater force is required to detach the particle if a normal, rather than tangential, force is applied. At high receptor densities, tangential forces can be as much as 56 times more disruptive than normal forces in removing cells from surfaces. The higher sensitivity to tangential forces is because body forces exerted tangentially are focused on bonds at the back edge of contact and because the ratio of bond length to bead radius is small, which constrains the bonds in an orientation near to normal to the substrate and results in large axial bond tensions. Hydrodynamic shear, and with its associated torque, is only slightly more disruptive than a tangential force of the same magnitude. Forces applied at an angle to the substrate from 0 degrees (tangent) to 80 degrees are as effective as a tangential force at detaching a particle. Our simulations provide a rational means for comparing the results between different adhesion assays.