The neointimal tissue characteristics inside sirolimus-eluting stent (SES) were evaluated by optical coherence tomography (OCT) according to follow-up duration. One hundred and thirty-three Optical coherence tomography was performed in 96 patients with 143 SES which were retrospectively included and divided into 2 groups according to follow-up duration: Group 1, <24 months (98 stents in 71 patients); Group 2, >24 months (35 stents in 25 patients). The neointimal tissue coverage pattern and characteristics were studied using a new OCT analysis system which can quantitatively analyze tissue property by measuring attenuation, backscatter and signal intensity in the region of interest. Using these parameters, a multivariable logistic regression model was constructed to divide neointima into homogenous or heterogeneous type. We defined homogeneous nointima as neointimal tissue having uniform optical properties and does not showing focal variations in backscattering pattern and heterogeneous neointima as neointimal tissue with focally changing optical properties and showing various backscattering patterns. The average time between stent implantation and follow-up OCT imaging was 1.2 years in Group 1 and 3.2 years in Group 2. The number of neointima covered cross-sections, neointimal thickness, and neointimal area increased significantly with the length of follow-up duration after SES implantation (P < 0.01). The incidence of heterogeneous neointima was higher in Group 2 than in Group 1 (P < 0.01). Heterogeneous neointima was associated with higher incidence of microvessels (P = 0.0023) and lipid rich plaque (P = 0.0015) compared with homogeneous neointima. The neointimal tissue characteristics may change over time after SES implantation. The incidence of heterogeneous pattern was higher in the SES group with longer follow-up duration. Microvessels and lipid rich plaques were more frequently observed in neointima with heterogeneous pattern. Neointimal heterogeneity could be an important factor for the late stability of SES.