Novel polymer-free drug-eluting stents have been developed to reduce polymer-related adverse events. However, neointimal coverage after polymer-free DES implantation is unclear and validation between optical coherence tomography (OCT) and histology is required. Sixteen polymer-free sirolimus-eluting stents were randomly implanted into coronary arteries of 8 normal swine. OCT and histological measurement were conducted at 3 or 6 months after stent placement. For quantitative measures, lumen area, stent area, neointimal area and neointimal thickness were validated in every single OCT and histology matched cross-section. Moreover, for qualitative analysis, OCT signal patterns of neointimal tissue were classified as homogeneous, layered and heterogeneous patterns based on optical intensity and backscatter pattern and peri-strut inflammation was also determined by histology. In total, 70 OCT and histology matched cross-sections were analyzed. At quantitative analysis, good correlations and agreements were found in the measurement of lumen area (ICC = 0.67, P<0.001), neointimal area (ICC = 0.89, P<0.001) and neointimal thickness (ICC = 0.94, P<0.001) except for stent area (ICC 0.19, P = 0.13) between OCT and histology. At qualitative analysis, lymphocyte infiltrations of peri-strut were more frequently seen in heterogeneous sections than in homogeneous sections (10/14 sections, 71.4% vs. 12/50 sections, 24%; P = 0.003). In conclusion, OCT has proper correlation and agreement with histology in assessment of neointimal formation and heterogeneous neointima assessed by OCT may also be associated with peri-strut inflammation detected in histology after polymer-free sirolimus-eluting stents implantation, supporting the use of OCT to evaluate neointimal coverage after polymer-free stent implantation in clinical practice.