A multi-part substitution infusion fluid for an extracorporeal blood treatment and methods for using same are provided. Generally, the multi-part substitution fluid comprises a first solution composed of electrolites but without divalent cations and a second solution comprising divalent cations. Another embodiment includes a third solution comprising a matching citrate/citric acid anticoagulant. The described methods of using the multi-part substitution infusion fluids significantly reduce risks associated with various extracorporeal blood treatments.