AIMS: Plaque rupture and subsequent thrombosis is known to be the most important pathology leading to acute coronary syndrome (ACS). We investigated by optical coherence tomography (OCT) whether in ACS there is an association of the location of the culprit plaque in the coronary tree with plaque rupture and/or thin cap fibroatheroma (TCFA). METHODS AND RESULTS: We included 74 patients presenting with ACS that underwent OCT study of the culprit lesion. The distance of the culprit lesion from the ostium was measured angiographically, and the presence of rupture and/or TCFA was assessed by OCT. Sixty-seven patients were analysed. Forty-five ruptured plaques were identified by OCT (67.1%). The distance from the ostium was lower for culprit ruptured plaques versus culprit non-ruptured plaques (p<0.01), particularly in the left anterior descending (LAD) and the left circumflex (LCx) arteries. The majority of culprit ruptured plaques (68.9%) was located in the proximal 30 mm of the coronary arteries. A distance from the ostium of ≤30.54 mm predicted plaque rupture with 71.1% sensitivity and 68.2% specificity. Culprit lesions in the proximal 30 mm are associated with rupture (p<0.05), TCFA (p<0.05), and lower minimal cap thickness (p<0.05). CONCLUSIONS: Culprit ruptured plaques in ACS seem to be predominately located in the proximal segments of the coronary arteries.