To investigate age- and gender-related differences in non-culprit versus culprit coronary vessels assessed with virtual histology intravascular ultrasound (VH-IVUS).; In 390 patients referred for coronary angiography to a single center (Luzerner Kantonsspital, Switzerland) between May 2007 and January 2011, 691 proximal vessel segments in left anterior descending, circumflex and/or right coronary arteries were imaged by VH-IVUS. Plaque burden and plaque composition (fibrous, fibro-fatty, necrotic core and dense calcium volumes) were analyzed in 3 age tertiles, according to gender and separated for vessels containing non-culprit or culprit lesions. To classify as vessel containing a culprit lesion, the patient had to present with an acute coronary syndrome, and the VH-IVUS had to be performed in a vessel segment containing the culprit lesion according to conventional coronary angiography.; In non-culprit vessels the plaque burden increased significantly with aging (in men from 37% ± 12% in the lowest to 46% ± 10% in the highest age tertile, P < 0.001; in women from 30% ± 9% to 40% ± 11%, P < 0.001); men had higher plaque burden than women at any age (P < 0.001 for each of the 3 age tertiles). In culprit vessels of the lowest age tertile, plaque burden was significantly higher than that in non-culprit vessels (in men 48% ± 6%, P < 0.001 as compared to non-culprit vessels; in women 44% ± 18%, P = 0.004 as compared to non-culprit vessels). Plaque burden of culprit vessels did not significantly change during aging (plaque burden in men of the highest age tertile 51% ± 9%, P = 0.523 as compared to lowest age tertile; in women of the highest age tertile 49% ± 8%, P = 0.449 as compared to lowest age tertile). In men, plaque morphology of culprit vessels became increasingly rupture-prone during aging (increasing percentages of necrotic core and dense calcium), whereas plaque morphology in non-culprit vessels was less rupture-prone and remained constant during aging. In women, necrotic core in non-culprit vessels was very low at young age, but increased during aging resulting in a plaque morphology that was very similar to men. Plaque morphology in culprit vessels of young women and men was similar.; This study provides evidence that age- and gender-related differences in plaque burden and plaque composition significantly depend on whether the vessel contained a non-culprit or culprit lesion.