Activation of integrins by Mn is a benchmark in the integrin field, but how Mn works and whether it reproduces physiological activation is unknown. We show that Mn and high Mg concentrations compete with Ca at the ADMIDAS and shift the conformational equilibrium toward the open state, but the shift is far from complete. Additionally, replacement of Mg by Mn at the MIDAS increases the intrinsic affinities of both the high-affinity open and low-affinity closed states of integrins, in agreement with stronger binding of Mn than Mg to oxygen atoms. Mutation of the ADMIDAS increases the affinity of closed states and decreases the affinity of the open state and thus reduces the difference in affinity between the open and closed states. An important biological function of the ADMIDAS may be to stabilize integrins in highly discrete states, so that when integrins support cell adhesion and migration, their high and low affinity correspond to discrete on and off states, respectively.