Previous optical coherence tomography (OCT) studies in patients with drug-eluting stents (DESs)-related very late stent thrombosis (VLST) were scarce. Therefore, we investigated OCT findings of VLST after implantation of DESs. Using OCT, we analyzed the status of stent struts and neointimal characteristics in 18 patients who developed VLST after DES implantation. These results were compared to those in 57 patients with neointimal hyperplasia causing >40% diameter stenosis. Lipid-laden neointima was defined as a region with marked signal attenuation and a diffuse border. Four (22.2%) of 18 patients with VLST had ruptured and lipid-laden neointima inside DESs without uncovered or malapposed stent struts. In the remaining 14 patients who developed VLST without neointimal rupture, uncovered and malapposed struts were observed in nine and seven patients, respectively, and lipid-laden neointima in four patients. Lipid-laden neointima was more frequently observed in four patients with neointimal rupture than in 14 patients without neointimal rupture (100% vs. 28.6%, respectively, P = 0.023). Of 57 patients with neointimal hyperplasia, eight (14.0%) had lipid-laden neointima. Time to OCT study after DES implantation was significantly longer in the eight patients with lipid-laden neointima than in 49 patients without lipid-laden neointima (45.5 ± 17.7 months vs. 11.7 ± 7.2 months, respectively, P < 0.001). Lipid-laden neointima was detected in some patients with neointimal hyperplasia > 1 year after DES implantation. In addition to uncovered or malapposed struts, rupture of lipid-laden neointima inside DESs was identified in some patients with DES-related VLST.