Objective: Acute STEMI is often accompanied by reciprocal ST-segment depression (RC) occurring in opposite leads, whose significance has been debated for decades. The possible role of collateral circulation in promoting RC in acute STEMI has not been identified. So our aim to find the relationship between collateral circulation and RC in STEMI patients treated with primary percutaneous intervention (PPCI). Methods: The study included 112 pts. with acute STEMI underwent PPCI. The patients divided in to 2 groups: Group (A):66 pts. with RC, Group (B):46 pts without RC. All patients subjected to history taking, ECG [localization of infarction & RC], CKMB level, transthoracic echo [LVEF%], coronary angiography &PPCI to culprit artery and assess number of diseased vessels, site of occlusion, collaterals, TIMI flow pre and post PCI. Results: Patients in group A with RC had shorter time to door, P < 0.001; more frequent inferior infarctions, P < 0.001; had higher CKMB level, P < 0.001; higher LVEDD, P < 0.001; LVESD, P < 0.001and lower LVEF, P = 0.004; had multi vessel diseases P = 0.02, increase incidence of RCA as a culprit artery <0.001 compared to patients with no RC. Patients with RC had significantly higher incidence of proximal LAD occlusion, distal RCA and distal LCX compared to patients without RC. The percentage of change was 61.2 ± 12.35% for ST elevation and 50.5 ± 10.87% for reciprocal ST depression post PCI with significance difference between them, t = 3.035P = 0.0023.There was no significant correlation between collateral circulation and RC. We found four significant independent predictors of RC. They were inferior infarction (P = 0.024), RCA as a culprit vessel, (P = 0.034), low EF, (P = 0.007) and multi-vessel disease, (P = 0.022). Conclusion: There is no correlation between concomitant RC and presence of collateral vessels in acute STEMI patients. So the pathogenesis of reciprocal ST-segment changes result from an interplay of ischemia at distance due to multi-vessel CAD and benign mirror electrical changes not caused by collateral circulation diverting blood to ischemic area from non-diseased artery. Keywords: Collateral circulation; Primary PCI; Reciprocal ST depression; STEMI.