Optical coherence tomography (OCT) is a high resolution imaging modality and has been considered as the ideal tool for the evaluation of neointimal tissue and vascular responses following stent implantation. However, vascular response profiles following the implantation of a novel nano polymer-free sirolimus-eluting stent (SES) assessed by OCT has not been fully investigated. Therefore, the aim of the present study was to determine the effects of a nano polymer-free SES on neointimal formation using OCT. A total of 16 nano polymer-free SESs were implanted in the coronary arteries of 8 pigs. At 3(n=4) or 6 months (n=4), the animals were euthanized following OCT evaluation and the stented arterial segments were analyzed by histological analysis. Neointimal area, thickness and burden were evaluated by OCT. In addition, strut-associated inflammation, stent endothelialization and arterial injury were investigated by histomorphological analysis. OCT examination showed that at 6 months, neointimal thickness (193.3 +/- 109.5 vs. 167.2 +/- 119.7 mu m, P=0.023) and neointimal burden (29.3 +/- 14.3 vs. 24.8 +/- 17.4%, P=0.006) significantly increased compared with at 3 months. Histomorphological analysis indicated that the endothelialization score was significantly greater at 6 months compared with at 3 months (2.85 +/- 0.36 vs. 2.52 +/- 0.60, P< 0.001). However, at 3 months, nano polymer-free SES showed a significantly higher inflammatory score [0 (0, 1) vs. 0(0,0), P< 0.001] compared with at 6months. In conclusion, nano polymer-free SES achieves endothelialization at 3 months; however, neointimal proliferation is more significant at 6 months and may be attributed to strut-associated inflammation.