In the scenario with four quark generations, we perform a fit using flavor-physics data and determine the allowed values-preferred central values and errors-of all of the elements of the 4×4 quark-mixing matrix. In addition to the direct measurements of some of the elements, we include in the fit the present measurements of several flavor-changing observables in the K and B systems that have small hadronic uncertainties, and also consider the constraints from the vertex corrections to Z→bb̄. The values taken for the masses of the fourth-generation quarks are consistent with the measurements of the oblique parameters and perturbativity of the Yukawa couplings. We find that |Vtb|0.98 at 3σ, so that a fourth generation cannot account for any large deviation of |Vtb| from unity. The fit also indicates that all the new-physics parameters are consistent with zero, and the mixing of the fourth generation with the other three is constrained to be small: we obtain |Vub′|<0.06, |Vcb′|<0.027, and |Vtb′|<0.31 at 3σ. Still, this does allow for the possibility of new-physics signals in Bd, Bs and rare K decays. © 2011 American Physical Society.