An implantable stimulation system is provided for stimulation of the heart, phrenic nerve, gastric system, or other tissue structures accessible via a patient's upper gastrointestinal system or airway. The stimulation system includes an implantable controller housing including a pulse generator; at least one electrical lead attachable to the pulse generator; and at least one electrode carried by the electrical lead that is positionable and fixable within the upper gastrointestinal tract or airway. The controller housing may be adaptable for subcutaneous implantation, or within the upper gastrointestinal tract or airway, wherein the controller housing is proportioned to substantially permit fluid and solid flow through the upper gastrointestinal tract or airway about the controller housing. The pulse generator may be operable to deliver one or more electrical pulses effective in cardiac pacing, cardiac defibrillation, cardioversion, cardiac resynchronization therapy, diaphragm pacing, phrenic nerve stimulation, gastric electrical stimulation, or a combination thereof.