BACKGROUND: Raloxifene, a selective estrogen receptor modulator (SERM), decreases total and low-density lipoprotein cholesterol (LDL-C) in postmenopausal women and inhibits increases in intima-media thickness (IMT) in animal models. We tested whether up to 8 years exposure to raloxifene had an effect on subclinical atherosclerosis in the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) trial and the follow-up study, the 4-year Continuing Outcomes Relevant to Evista (CORE) trial. METHODS: A subsample of postmenopausal women with osteoporosis, who had completed the MORE and CORE trials and were on average 68 years of age and 19 years postmenopausal at randomization into MORE, participated in this substudy. Within 6 months of cessation of study drug in CORE, right common carotid artery IMT (CIMT) and carotid artery stiffness and arterial compliance were measured at one of two sites (San Diego and San Francisco) using high-resolution B-mode ultrasound. CIMT and arterial stiffness measures were compared between women who had received raloxifene vs. placebo; the primary analysis included only women who were >or=80% drug compliant and had used <or=6 months of lipid-lowering medication during CORE. RESULTS: For the primary analysis dataset (n = 89), there was no significant difference in mean CIMT between the raloxifene and placebo groups (0.83 and 0.81 mm, respectively, p = 0.62). Carotid artery stiffness and compliance were not significantly different between treatment groups (p = 0.33 and 0.59, respectively). CONCLUSIONS: These preliminary data suggest that in this self-selected group of elderly post-menopausal women with osteoporosis who were evaluated within 6 months of cessation of study medication, there were no differences between long-term raloxifene treatment and placebo groups in several measures of subclinical atherosclerosis.