OBJECTIVE: Intravascular ultrasound (IVUS) is a cornerstone tool for the diagnosis of plaque rupture (PR) but is usually used secondary to the suspicion of PR on angiography; the true incidence of PR may therefore be overestimated. We sought to evaluate predictors of angiographic diagnosis of PR using a non-angiographically driven IVUS examination. METHODS AND RESULTS: Diagnosis of PR on IVUS required agreement between two operators blinded to the results of angiography. Any irregular lesion with ulceration, flap or aneurysm on a qualitative angiogram was considered suspicious for PR. IVUS-detected PR and non-PR lesions were compared with the corresponding angiograms. A total of 224 distinct (ruptured or non-ruptured) lesions were detected by IVUS in 65 patients; 49 of the 105 IVUS-detected non-culprit PRs were suspected on angiography. The positive and negative predictive values for correct angiographic diagnosis of PR were 96% and 61%, respectively. Proximal coronary location, wide cavity, and counterflow rupture were strong predictors of correct angiographic diagnosis, enabling four specific angiographic patterns to be identified using three-dimensional IVUS PR reconstruction. CONCLUSION: Against IVUS as the gold standard, angiographic diagnosis of PR showed good specificity but low sensitivity. However, better angiographic diagnosis should enable medical treatment to be optimized, especially with respect to statin therapy.