Objectives: Barrett’s esophagus (BE) is the only known precursor to esophageal adenocarcinoma. Data examining the association of aspirin with the onset of BE, particularly for women, are scant and conflicting. Methods: We leveraged data from 121,700 women enrolled in the Nurses’ Health Study, a large prospective cohort study, who biennially provided detailed information regarding endoscopy and use of aspirin. We used unconditional logistic regression to obtain multivariable (MV)-adjusted odds ratios (ORs) and 95% confidence intervals (CI) to estimate the risk of BE in regular aspirin users (≥2 times/week) compared to non-regular users. Results: Among 27,881 women who had undergone upper GI endoscopy, we documented 667 BE cases over 18 years of follow-up. Compared to non-regular users, women who regularly used aspirin had a MV-adjusted OR for BE of 0.85 (95%CI: 0.72, 0.99). The corresponding OR was 0.73 (95%CI: 0.56, 0.96) for BE at least 1 cm long. Compared with women who did not use any aspirin, the MV-adjusted OR for any BE was 0.91 (95% CI, 0.69, 1.20) for women taking 0.5-1.5 tablets/week; 0.92 (95%CI 0.76, 1.11) for 2–5 tablets/week; and 0.71 (95%CI 0.55, 0.92) for ≥6 tablets/week (p-trend=0.01). Compared with non-regular users, the MV-adjusted OR for BE risk was 0.90 (95%CI 0.67, 1.20) for women who regularly used aspirin for 1–5 years, 0.84 (95%CI 0.65, 1.09) for 6–10 years, and 0.81 (95%CI 0.67, 0.97) for >10 years (p-trend=0.03). Conclusion: Regular aspirin use was associated with a reduction in the risk of Barrett’s esophagus in women. The reduction in risk appeared related to higher dose and longer duration of use
