The authors conducted a prospective cohort analysis in the Women's Health Study (1992–2004), a completed randomized trial assessing aspirin and vitamin E in the primary prevention of cancer and cardiovascular disease, to evaluate use of oral conjugated estrogen alone (0.625 mg/day) and breast cancer risk in a time-varying fashion. Over an average of 10 years of follow-up, 305 incident cases of breast cancer (258 invasive and 47 in situ cancers) were documented among 12,718 women aged 45 years or more who were either consistent current users of oral conjugated estrogen alone (0.625 mg/day) or never users of any type of postmenopausal hormones at baseline and during follow-up. The multivariable hazard ratios comparing “consistent current users” with “never users” were 1.11 (95% confidence interval: 0.79, 1.56) for total breast cancer and 1.13 (95% confidence interval: 0.77, 1.64) for invasive cases. No significant associations were observed for use of less than 8 and 8 years or more. Restricting the analyses to women with prior hysterectomy somewhat strengthened the associations, albeit still not significantly. These data, like those from the Women's Health Initiative, show no significant increase in breast cancer risk with use of oral conjugated estrogen alone (0.625 mg/day), but a small increase or decrease in risk cannot be excluded.