Context. - Gestational diabetes mellitus (GDM) affects 3% to 5% of pregnancies. Knowledge of risk factors for GDM is needed to identify possible preventive strategies. Objective. - To assess whether recognized determinants of non-insulin dependent diabetes mellitus also may be markers for increased risk of GDM. Design. - Prospective cohort study. Setting. - The Nurses' Health Study II, which involves female US nurses aged 25 to 42 years at entry. Participants. - The analyses included 14 613 women without previous GDM or other known diabetes who reported a singleton pregnancy between 1990 and 1994. Of these women, 722 (4.9%) reported a new diagnosis of GDM. Main Outcome Measure: Self-report of GDM, validated by medical record review in a subset. Results. - In multivariate analyses including age, pregravid body mass index (BMI), and other GDM risk factors, the risk for GDM increased significantly with increasing maternal age (P for trend, <.01) and family history of diabetes mellitus (relative risk, 1.68: 95% confidence interval [CI], 1.39-2.04). Relative risks for GDM were 2.13 (95% CI, 1.65-2.74) for pregravid BMI of 25 to 29.9 kg/m2 and 2.90 (95% CI, 2.15-3.91) for BMI of 30 kg/m2 or more (vs BMI of <20 kg/m2). Risk for GDM increased with greater weight gain in early adulthood, and it also increased among nonwhite women. Pregravid current smokers had a relative risk for GDM of 1.43 (95% Cl, 1.14- 1.80), and pregravid vigorous exercise was associated with a non-significant reduction in GDM risk. Conclusions. - Advanced maternal age, family history of diabetes mellitus, nonwhite ethnicity, higher BMI, weight gain in early adulthood, and cigarette smoking predict increased GDM risk. These observations may facilitate the identification of women at particular risk for GDM and suggest potential strategies for reducing this risk even before a woman becomes pregnant, such as avoiding substantial weight gain and smoking.