In the United States alone, there are approximately 250,000 people living with solid organ transplants. Significant improvements have occurred in postoperative management with rejection remaining the major determinant of outcome. The current gold standard in surveillance of cardiac allograft rejection remains the catheter based endomyocardial biopsy (EMB). For early detection of rejection, surveillance biopsies are performed at regular intervals. These invasive tests are unpleasant for the patient, expensive for the patient and healthcare system, subject to sampling error, and can be a lagging indicator of organ damage. Donor specific cell free DNA (cf-DNA) increases in patients with solid organ rejection. We have developed a non-invasive assay which can discriminate “self-specific” cf-DNA from donor specific cf-DNA from a small blood sample from the patient. This allows for accurate, frequent, and inexpensive routine monitoring and provides an early indication of organ injury.