The incidences of esophageal adenocarcinoma and squamous cell carcinoma (SCC) are higher in males than in females. We investigated whether female-related hormonal factors are associated with risks of these two types of esophageal cancer. We examined the association between use of hormone therapy (HT) and the risks of esophageal adenocarcinoma and SCC in postmenopausal women enrolled in the Women's Health Initiative (WHI) clinical trials and observational studies. Twenty-three esophageal adenocarcinoma and 34 esophageal SCC cases were confirmed among the 161,080 participants, after a median of 11.82 years of follow-up. Risk of esophageal SCC was lower among HT users (past users: HR = 0.25, 95% CI: 0.06-1.10 in 2 cases; current users: HR = 0.41, 95% CI: 0.18-0.94 in 9 cases). A decreased esophageal SCC risk was observed for current users of estrogen plus progestin (E+P) therapy (HR = 0.25, 95% CI: 0.07-0.86 in 3 cases) but not for current users of estrogen-only therapy (HR = 0.96, 95% CI: 0.28-3.29 in 6 cases). No association was observed between the use of HT and the risk of esophageal adenocarcinoma. No other reproductive or hormonal factors were significantly associated with the risk of either SCC or adenocarcinoma. Current use of E+P therapy was found to be associated with a decreased risk of esophageal SCC, but no association was observed with esophageal adenocarcinoma. To provide more definitive evidence, a pooled analysis of all available studies or a much larger study would be needed.