A multi-fluid injector system and methods of operation thereof are presented. One embodiment of such a fluid injector system includes an automatic refill procedure for a fluid injector system comprising a fluid injector and an operably engaged syringe. The procedure includes the step of determining, using an electronic control device operably controlling the fluid injector system, whether a fluid injection procedure involving the syringe is impending. If the electronic control device determines that the fluid injection procedure is not impending, such that the automatic refill will not interfere with the fluid injection procedure, an automatic refill of the syringe is initiated.