Background: This study examined the association between reproductive lifespan and incident type 2 diabetes mellitus (T2DM) and hypertension in mid-age women. Also, the combined effect of reproductive lifespan and body mass index (BMI) on the risks of T2DM and hypertension were explored. Methods: Reproductive lifespan was defined as the difference between age at menopause and age at menarche, and categorized as < 35, 35-37, 38-40, and >= 41 years based on the quartile distribution. A multivariable Cox proportional hazard regression was used, adjusting for socio-demographic, lifestyle, and reproductive factors. Results: Of 6357 postmenopausal women included (mean [SD] age at last follow-up, 66.3[3.3] years), a total of 655 developed incident T2DM (10.3%) and 1741 developed hypertension (30.0%) during 20 years of follow-up. The total sample had a mean (SD) reproductive lifespan of 37.9 (4.5). Compared with the women who had a reproductive lifespan of 38-40 years, those with a short reproductive lifespan (< 35 years) had a 30% increased risk of T2DM and twice the risk of hypertension. Under the combined model, women who had a short repro-ductive lifespan (< 35 years) and who had a BMI >= 30 kg/m(2) at baseline showed a higher risk of T2DM (HR: 6.30, 95% CI: 4.41-8.99) and hypertension (HR: 6.06, 4.86-7.55) compared with women who had a reproductive lifespan of 38-40 years and a BMI < 25 kg/m(2). Conclusions: A higher risk of both incident T2DM and hypertension at midlife was found among women experiencing a shorter reproductive lifespan, with pronounced risk for women experiencing both a short reproductive lifespan (< 35 years) and a higher baseline BMI (>= 30 kg/m(2)). Women with a short reproductive lifespan may benefit from maintaining healthy body weight in midlife.