We explore whether racial differences in a United States population influence disease prevalence and perinatal outcome in gestational diabetes mellitus (GDM). The data presented are based on 3744 consecutive patients who underwent universal screening at 24–28 wk gestation; those with a 1-h plasma glucose ≥7.2 mM underwent a 100-g 3-h oral glucose tolerance test (OGTT). The overall prevalence of GDM was 3.5 cases/100 with the standard O'Sullivan-Mahan diagnostic criteria derived for plasma, whereas use of the Carpenter-Coustan modification of the O'Sullivan-Mahan criteria yielded a prevalence of 5.5. The population was 39.1% white, 37.7% black, 19.8% Hispanic, and 3.45% Oriental/other. For those patients with a nondiagnostic test, mean plasma glucose at each time point of the OGTT was similar for all racial groups. Because of demographic and phenotypic heterogeneity between different racial groups, the influence of these different variables on the prevalence of GDM was tested by multiple logistic regression. Black and Hispanic race, maternal age, and percentage ideal body weight were found to have significant independent effects on the prevalence of GDM (P < 0.05, 0.001, 0.001, and 0.001, respectively). The adjusted relative risk of GDM was significantly higher in black (1.81, 95% confidence interval [;CI] 1.13–2.89, P < 0.05) and Hispanic (2.45, 95% CI 1.48–4.04, P < 0.001) patients compared with whites. The influence of race on infant birth weight was examined in the 92 patients with GDM controlled with diet. Despite comparable degrees of carbohydrate intolerance across racial groups, mean birth weight was found to be highest in Hispanics and lowest in blacks and Orientals. By analysis of covariance, race was found to have a significant independent effect on birth weight (P = 0.017), with maternal percentage ideal body weight a significant covariate (P = 0.009). These results suggest that race as well as maternal age and degree of obesity must be taken into account when comparing the prevalence of GDM in different populations and assessing the impact of specific therapeutic interventions on perinatal outcome.