OBJECTIVES This study sought to investigate the impact of longitudinal lesion geometry on the location of plaque rupture and clinical presentation and its mechanism. BACKGROUND The relationships among lesion geometry, external hemodynamic forces acting on the plaque, location of plaque rupture, and clinical presentation have not been comprehensively investigated. METHODS This study enrolled 125 patients with plaque rupture documented by intravascular ultrasound. Longitudinal locations of plaque rupture were identified and categorized by intravascular ultrasound. Patients' clinical presentations and TIMI (Thrombolysis In Myocardial Infarction) flow grade in an initial angiogram were compared according to the location of plaque rupture. Longitudinal lesion asymmetry was quantitatively assessed by the luminal radius change over the segment length (radius gradient [RG]). Lesions with a steeper radius change in the upstream segment compared with the downstream segment (RG(upstream) > RG(downstream)) were defined as upstream- dominant lesions. RESULTS On the basis of the site of maximum rupture aperture, 56.0%, 16.0%, and 28.0% of the patients had upstream, minimal lumen area, and downstream rupture, respectively. Patients with upstream rupture more frequently presented with ST- segment elevation myocardial infarction (45.7%, 40.0%, 22.9%; p = 0.030) and with TIMI flow grade < 3 (32.9%, 20.0%, 17.1%; p = 0.042). According to the ratio of upstream and downstream RG, 69.5% of lesions were classified as upstream- dominant lesions, and 30.5% were classified as downstream-dominant lesions. Among the 66 upstream- dominant lesions, 65 cases (98.5%) had upstream rupture, and the RG ratio (RG(upstream)/RG(downstream)) was an independent predictor of upstream rupture (odds ratio: 1.481; 95% confidence interval: 1.035 to 2.120; p = 0.032). Upstream-dominant lesions more frequently manifested with ST- segment elevation myocardial infarction than did downstream-dominant lesions (48.5% vs. 24.1%; p = 0.026). CONCLUSIONS Both clinical presentation and degree of flow limitation were associated with the location of plaque rupture. Longitudinal lesion asymmetry assessed by RG, which can affect regional distribution of hemodynamic stress, was associated with the location of rupture and with clinical presentation. (C) 2017 by the American College of Cardiology Foundation.