The purpose of the study was to explore the association of menstrual and reproductive factors with thyroid nodules in Chinese women older than 40 years of age. A questionnaire was completed by 6,571 women aged 40 years or older in a community-based epidemiological investigation of thyroid nodules conducted from June to November 2011 in Nanjing City. Thyroid nodules were measured by ultrasound. The Thyroid Imaging Reporting and Data System score was used to differentiate between benign and possibly malignant nodules. Menopausal age (>55 vs. <50 years: RR = 1.17, 95 % CI 1.00-1.34) and number of reproductive years (>40 vs. <35 years: RR = 1.12, 95 % CI 1.01-1.24) increased the risk of thyroid nodules, but were not associated with suspected malignant nodules. Women who experienced more pregnancies (≥5 vs. ≤1: RR = 2.09, 95 % CI 1.79-2.40) and abortions (≥3 vs. 0: RR = 1.61, 95 % CI 1.41-1.81) were prone to development of thyroid nodules, and more likely to form suspected malignant nodules (pregnancies, RR = 3.59, 95 % CI 1.60-7.20; abortions, RR = 2.36, 95 % CI 1.31-4.06). Furthermore, higher risks of thyroid nodules (RR = 1.36, 95 % CI 1.14-1.59) and suspected malignant nodules (RR = 2.80, 95 % CI 1.08-6.53) were observed in women who had undergone artificial compared with natural abortion. Periods of elevated estrogen and progesterone levels in women, such as pregnancy, were the key occasions for occurrence of both benign and suspiciously malignant thyroid nodules, while longer lifetime length of exposure to female sex hormones might promote the growth of thyroid nodules.