Exercise training (EX) following percutaneous transluminal coronary angiography (PTCA) reduces progression to restenosis and increases event-free survival rates. Our aim was to determine whether EX inhibits lesion development and/or alters the extracellular matrix (ECM) composition of the neointima (NI) in a porcine PTCA model. Miniature Yucatan swine were assigned to cage confinement (SED) or EX for 20 wk. After 16 wk, all animals underwent a PTCA procedure of the left anterior descending artery (LAD) and left circumflex artery (LCX), with subsequent placement of an externalized jugular catheter. Animals recovered for 2 days and then resumed the previous protocol of SED or EX. Twelve days following PTCA, all animals received an intravenous bromodeoxyuridine (BrdU) injection to label proliferating cells. At 28 days following PTCA, the animals were euthanized, the LAD and LCX excised, and underwent standard histological processing for total collagen, type I collagen, fibronectin, BrdU, and Verhoeff-van Gieson stain. Our results demonstrate that EX significantly decreased lesion size and NI proliferation (-48%) in the LAD (P < 0.05) but not the LCX. Furthermore, EX attenuated type I collagen expression only in LAD, whereas total collagen was increased (5.9%) and fibronectin was decreased (-7.9%) in the NI of both vessels (P < 0.05). In conclusion, EX following PTCA may increase event-free survival rates following PTCA by decreasing lesion size and altering ECM composition.