Purpose: Neoatherosclerosis within a stent has been recently described as a culprit of late stent failure. We investigated by optical coherence tomography (OCT) the association of neoatherosclerotic plaque morphology with neointimal rupture (NR) and clinical presentation in patients late after coronary stent implantation. Methods: From 1/1/2007 to 31/1/2012, 74 patients from two institutions underwent OCT assessment of a coronary stent implanted at least 18 months prior to OCT study. Native atherosclerosis criteria were used for neointimal characterization. Results: Neoatherosclerosis was observed in 59.5% of the stents (n=44). Stents with neoatherosclerosis were more often associated with symptoms compared to stents without neoatherosclerosis (59.1% acute coronary syndrome (ACS), 25% stable angina (SA), and 15.9% asymptomatic versus 43.3% ACS, 6.7% SA, 50% asymptomatic, p<0.01). Among neoatherosclerotic lesions (n=44), NR was detected in 19 (43.2%) and had higher incidence in ACS (61.5%) than in SA (18.2%) and asymptomatic (14.3%) (p<0.05). Thrombus was detected in all NR cases. Fibrous cap thickness was lower in NR lesions compared to lesions without NR (48±21 μm versus 104±58μm, p<0.01). Lipid content tended to be higher in lesions with NR (260±103° versus 203±85°, p=0.051). Lesions with NR had more often dense macrophage infiltration (84.2% versus 44.0%, p<0.05). There were no differences in neovascularization or calcifications between lesions with or without NR. Conclusions: Neoatherosclerosis is frequent and more common among symptomatic patients. Importantly, neointimal rupture is associated with ACS late after stent implantation. Specific morphological characteristics, such as cap thickness and macrophage infiltration are associated with rupture of neoatherosclerotic plaques.