Systems and methods for calibrating an orientation of an implantable device in a patient is described. An exemplary system includes a calibration circuit that can receive acceleration information sensed from an implantable medical device (IMD) implanted in a patient, and receive reference acceleration information sensed from a reference device associated with the patient. The acceleration information and the reference acceleration information are acquired when the patient assumes a first posture or in a first position. The calibration circuit determines a spatial relationship between an orientation of the IMD and a reference orientation of the reference device using the received acceleration information and the received reference acceleration information, and calibrate subsequent acceleration information sensed from the IMD using the determined spatial relationship to correct for the orientation of the IMD.