Background: All plaques that trigger acute coronary syndromes (ACS) present various characteristics of vulnerability. However, not all vulnerable plaques (VP) lead to an ACS. This raises the question as to which of the established CT vulnerability features hold the highest probability of developing ACS. Aim: To identify the distinct phenotype of VP that exposes the unstable atheromatous plaque to a higher risk of rupture. Material and Methods: In total, 20 patients in whom cardiac computed tomographic angiography (CCTA) identified the presence of a vulnerable plaque and who developed an ACS within 6 months after CCTA examination were enrolled in the study, and compared to 20 age- and gender-matched subjects with VPs who did not develop an ACS. All included patients presented VPs at baseline, defined as the presence of minimum 50% degree of stenosis and at least one CT marker of vulnerability (low attenuation plaques [LAP], napkin-ring sign [NRS], positive remodeling [PR], spotty calcifications [SCs]). Results: The two groups were not different in regards to age, gender, cardiovascular risk factors, and comorbidities. Patients who developed an ACS at six months presented higher volumes of lipid-rich (p = 0.01) and calcified plaques (p = 0.01), while subjects in the control group presented plaques with a larger fibrotic content (p = 0.0005). The most frequent vulnerability markers within VPs that had triggered ACS were LAPs (p <0.0001) and PR (p <0.0001). Multivariate analysis identified LAP as the strongest independent predictor of ACS at 6 months in our study population (OR 8.18 [1.23-95.08], p = 0.04). Conclusions: VPs producing an ACS exhibit a different phenotype compared to VPs that remain silent. The CCTA profile of VPs producing an ACS includes the presence of low attenuation, positive remodeling, and lipid-rich atheroma. The presence of these features in VPs identifies very high-risk patients, who can benefit from adapted therapeutic strategies in order to prevent an ACS.