We introduce the B-spline interpolation problem corresponding to a C∗-valued sesquilinear form on a Hilbert C∗-module and study its basic properties as well as the uniqueness of solution. We first study the problem in the case when the Hilbert C∗-module is self-dual. Passing to the setting of Hilbert W∗-modules, we present our main result by characterizing when the spline interpolation problem for the extended C∗-valued sesquilinear form has a solution. Finally, solutions of the B-spline interpolation problem for Hilbert C∗-modules over C∗-ideals of W∗-algebras are extensively discussed.