<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> To test the hypothesis of general atherosclerotic plaque destabilization during acute coronary syndrome (ACS), the present study sought to analyze the 3 coronary arteries by systematic intravascular ultrasound scan (IVUS). </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> Seventy-two arteries were explored in 24 patients referred for percutaneous coronary intervention after a first ACS with troponin I elevation. Fifty plaque ruptures (mean, 2.08 per patient; range, 0 to 6) were diagnosed by the association of a ruptured capsule with intraplaque cavity. Plaque rupture on the culprit lesion was found in 9 patients (37.5%). At least 1 plaque rupture was found somewhere other than on the culprit lesion in 19 patients (79%). These lesions were in a different artery than the culprit artery in 70.8% and were in both other arteries in 12.5% of these 24 patients. Complete IVUS examination of all 3 coronary axes in patients who had experienced a first ACS revealed that multiple atherosclerotic plaque ruptures were detected by IVUS; these multiple ruptures were present simultaneously with the culprit lesion; they were frequent and located (in three quarters of cases) on the 3 principal coronary trunks; and the multiple plaque ruptures in locations other than on the culprit lesion were less severe, nonstenosing, and less calcified. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusion—</jats:italic> </jats:bold> Although one single lesion is clinically active at the time of ACS, the syndrome seems nevertheless associated with overall coronary instability. </jats:p>