Aims: We aimed to study sex differences in coronary plaque burden and plaque composition in patients with coronary artery disease (CAD). Methods and results: Virtual histology intravascular ultrasound (VH-IVUS) and near-infrared spectroscopy (NIRS) imaging of a non-culprit coronary artery was performed in 178 (23.5%) women and 581 (76.5%) men who underwent invasive management of stable angina pectoris (SAP) or acute coronary syndrome (ACS). Women were older and had a worse cardiovascular risk profile than men, but less extended angiographic coronary disease. Irrespective of the presenting diagnosis, women had lower VH-IVUS-derived plaque burden than men (38.1% vs. 40.5% in SAP, and 35.9% vs. 38.8% in ACS). Standardised (mean 211 vs. 263 mm3 in SAP, and 199 vs. 245 mm3 in ACS) total plaque volume was lower in women. Volumes of fibrous tissue, fibro-fatty tissue, necrotic core and dense calcium were also lower in women. NIRS-derived lipid core burden index (LCBI) was lower in women, in particular in SAP (mean LCBI in the worst 4 mm 220 vs. 240). The observed differences remained significant after adjustment for clinical characteristics. Conclusions: Women had more favourable plaque characteristics than men, despite their worse risk profile. Long-term follow-up studies are required to evaluate the clinical consequences.