A detailed analysis of the anatomic relationships of the site of culprit lesions that have resulted in acute coronary syndromes (ACS) has not been reported.Coronary angiograms of consecutive patients who presented with ACS were analyzed according to multiple anatomic criteria.In left anterior descending artery (LAD) (n = 85), 85% of culprit lesions were located in the first 40 mm from the ostium. The presence of angulation on the lesion increased the risk of an ACS 1.92 times (95% confidence interval [CI] 1.9-3.07), and the presence of bifurcation after the lesion increased the risk 1.65 times (95% CI 1.04-2.62). Angulated lesions located within the first 40 mm from the ostium and before a bifurcation presented an 11-fold increased risk for an ACS. In right coronary artery (RCA) (n = 58), the risk of plaque rupture was almost 2.5 times higher in lesions located between 10 and 50 mm from the ostium compared to those located in 90-130 mm (relative risk [RR] 2.38, 95% CI 1.25-4.56). In left circumflex (LCx) (n = 40), the risk of plaque rupture was almost 4.5 and 5 times higher in the first 20 mm, and between 20 and 40 mm from the ostium, respectively, compared to 60 and 80 mm (relative risk [RR] 4.58, 95% CI 1.01-20.68 for 0-20 mm, and RR 4.95, 95% CI 1.14-21.47 for 20-40 mm) after adjustment for the presence of curve on the lesion. The presence of lesion angulation increased the risk of plaque rupture almost three times (RR 3.22, 95% CI 1.49-6.93).Specific anatomic features of the coronary arteries predispose to development and/or subsequent rupture of vulnerable plaques.