The main way to detect heart transplant rejection is endomyocardial biopsy (EMB), an invasive and time/money consuming procedure. This study was performed to consider diagnostic value of the newly emerged trans-thoracic tissue Doppler echocardiography (TDI) indices in detection of heart transplant rejection. Twenty consecutive transplant recipients were simultaneously assessed by EMB and TDI at certain intervals from the surgery. 50 TDI studies and 50 EMBs were performed totally. The results were analyzed to determine the relation between TDI values (“Strain” and “Time to Systole”) and histopathological rejection. Accuracy of these indices in diagnosis of rejection was also computed. Histopatohological exam revealed no significant rejection in 31 and significant rejection in 19. Septum “Strain” was significantly reduced with rejection; 11.8 versus 15.9 in non-rejecting group (P<0.01). There was also a significant reduction in Septum “Time to Systole” in rejected hearts; 72.7ms vs. 85.7ms in not-rejected hearts (P<0.01). Accuracy of septal indices was better than right ventricular or Lateral “Strain” and “Time to Systole” for detection of allograft rejection. In conclusion, These results suggest that Strain TDI has the potential to be used as a complementary or alternative method for detection of heart transplant rejection. Septal indices are more accurate than others. More investigations are needed to confirm this capability and also to determine the best applying schedule.