The objective of this study was to determine if early pregnancy maternal plasma lipid concentrations are elevated in women who later developed gestational diabetes mellitus (GDM) as compared with women who do not. Women, recruited prior to 16 weeks gestation, were followed until delivery. Maternal plasma lipid concentrations were measured in samples collected at 13 weeks gestation on average. Generalized linear models were used to estimate relative risks (RR) and 95% confidence intervals (95% CI). 5.5% of the cohort (47/851) developed GDM. Elevated triglyceride (TG) was positively associated with GDM risk (p for trend <0.001). After adjusting for maternal pre-pregnancy adiposity and other confounders, women with TG concentrations > or =137 mg/dl experienced a 3.5-fold increased risk of GDM (95% CI: 1.1-10.5) as compared with women who had concentrations <96 mg/dl. We noted a linear component of trend in risk of GDM with increasing plasma TG. Each 20mg/dl increase in TG was associated with a 10% increase in GDM risk (RR=1.1; 95% CI: 1.0-1.3). Associations between GDM risk and plasma concentrations of other lipids (i.e., total cholesterol, high-density lipoprotein, and low-density lipoprotein) were not evident. Larger prospective studies are needed to confirm our findings and to identify modifiable determinants of pregnancy-associated dyslipidemia.