Postmenopausal hormone therapy has been associated with an increased risk of venous thromboembolism (VT), including deep vein thrombosis and pulmonary embolism, in observational studies and secondary prevention clinical trials. The Women's Health Initiative (WHI) estrogen trial enrolled 10 739 women without a uterus aged 50 to 79 years. Participants were randomized to receive conjugated equine estrogen (0.625 mg/d) or placebo. Over an average of 7.1 years, VT occurred in 111 women randomized to estrogen and in 86 women randomized to placebo (hazard ratio [HR], 1.32). Deep VT was reported in 85 women randomized to estrogen and in 59 women randomized to placebo (HR, 1.47). There were no significant interactions between estrogen use and age, body mass index, or most other VT risk factors. Compared with WHI VT findings for estrogen and previous WHI findings for estrogen plus progestin, the HR for estrogen plus progestin was significantly higher than that for estrogen alone (P = .03), even after adjusting for VT risk factors. An early increased VT risk was associated with use of estrogen, especially within the first 2 years, but this risk elevation was less than that for estrogen plus progestin.