INTRODUCTION: Previous reports have noted associations between subfertility in women and increased risk of cardiovascular disease (CVD) events in later life. However, reports conflict regarding the associations between subfertility and CVD risk factors. Using data from a population-based cohort of Black and White women, we examined the association between longitudinal assessments of CVD risk factors and subfertility. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective cohort of Black and White women who have undergone repeated assessment of CVD risk factors beginning at study baseline (1985-1986). Risk factors included cigarette smoking, body mass index (BMI), blood pressure, lipid levels, glucose, and C-reactive protein. At approximately 40 years of age, an ancillary study assessed histories of subfertility. We used generalized estimating equations with a logit link model to examine associations between subfertility (dependent variable) and repeated CVD risk factors (independent variables), with adjustment for age, race, center, and education level in 1107 women. RESULTS: Cigarette use and higher levels of BMI, glucose, and triglycerides and lower levels of high-density lipoprotein cholesterol (HDL) were associated with subfertility after adjustment for age, race, and education. In multivariable models which included all of these risk factors, cigarette use (odds ratio [OR] 1.004, 95% confidence interval [CI] 1.002, 1.006, p<0.0001) and HDL (OR 0.99, 95% CI 0.99, 0.995, p=0.046) were still associated with subfertility, but associations with BMI, glucose, and triglycerides were no longer significant. CONCLUSIONS: Women with subfertility histories have adverse CVD risk factors across the reproductive lifespan. Cigarette use is a strong risk factor for infertility.