Estradiol has been shown to reduce neointima formation after balloon injury in rat carotid arteries. This study examines the effect of 17-β estradiol on neointima formation after balloon injury in swine coronary arteries, a model more similar to human restenosis. Twenty-one pigs (11 castrated males and 10 intact females) were randomized to treatment or control groups. Thirty day sustained release pellets containing either 1400 mg of 17-β estradiol or placebo were implanted subcutaneously. Six days after pellet implantation, animals underwent angioplasty of the circumflex artery. Five inflations to 10 atm for 30 sec were performed with compliant balloons. Pigs were sacrificed 2 weeks after balloon injury, and the coronary arteries removed. Histologic sections were stained with trichrome and digitized. Areas were calculated utilizing a morphometric analysis program. Each artery was assigned an injury score based on the extent and severity of injury present Results (mean ± SEM): ♂ estradiol ♂ placebo ♀ estradiol ♀ placebo n=5 n=6 n=5 n=5 intima area (mm2) 0.46±0.14 0.95±0.10 ** 0.37±0.11 1.01±0.12 *** intima thickness (μm) 467±52 614±68 ** 207±136 448±74 * injury score (0-3) 1.59±0.24 1.64±0.21 1.86±0.09 1.96±0.07 serum estradiol 1003±130 <15 **** 605±121 <15 **** (pg/ml) * p<0.05, ** p<0.02, *** p<0.005, **** p<0.001 estradiol vs. placebo 17-β estradiol reduces neointima formation after balloon injury of the coronary artery in male and female pigs. This intervention may be useful in the prevention of restenosis in patients.