Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) define neointima as the tissue encompassed between the stent and the lumen boundaries. This approach differs from the gold-standard histopathology, where neointima is traditionally calculated as the tissue between the internal elastic lamina (IEL) and the lumen. We aimed to investigate whether the neointimal assessment using IVUS and OCT-like definitions would correlate with the traditional histopathological quantification of neointima. Histopathological analysis was obtained from a porcine model of 28-day coronary in-stent neointimal proliferation (n=13 bare stents). Traditional histopathology neointimal area (NIHPATH area) was calculated as the lumen area minus the IEL area, while the percent neointimal obstruction was defined as NIHPATH area divided by the IEL area. The IVUS/OCT-like neointima area (NIHIVUS/OCT area) was defined as the lumen area minus the stent area, while the percent neointimal obstruction was defined as NIHIVUS/OCT area divided by the stent area. The neointimal area as well as the percent obstruction were significantly correlated between histopathology and IVUS/OCT-like definitions (R(2)=0.89 and 0.95 respectively; P<0.01 for both). The average absolute difference between the IVUS/OCT-like and the pathology-like measurements was close to zero, however with a relatively wide dispersion (difference for neointimal area: 0.41 mm(2) [95% CI 1.72 to (-)0.90 mm(2)]; difference for percent neointimal obstruction: 2.5% [95% CI 11.5% to (-)6.5%]). The present findings support the use of stent area in replacement to IEL area, as in IVUS & OCT imaging protocols, for the calculation of neointimal parameters in experimental model of restenosis.