Abstract: Objective To investigate the combined effect of obesity and family history of diabetes on the incidence of hyperglycemia in Nanjing. Methods Population-based cross-sectional study was conducted on local residents aged 30 and above in Nanjing by a multi-stage stratified cluster sampling method. The subjects who were non-hyperglycemia in the baseline were selected for the three-year follow-up survey. Cox proportional hazards model was used to estimate the combined effect of obesity and family history of diabetes on the incidence of hyperglycemia. Results Of 2 900 subjects without hyperglycemia in baseline, 2 093 participated in the follow-up survey, and follow-up proportion was 72.2%. Three-year cumulative incidence of hyperglycemia was 7.5%, which was 6.4% in the subgroup without family history of diabetes/no obesity and 13.3% in the subgroup with family history of diabetes/obesity. By multivariable Cox regression model, the subgroup with family history of diabetes/no obesity (HR=1.63,95% CI:1.02-2.60,P=0.042) and with family history of diabetes/obesity (HR=2.37,95% CI:1.36-4.13,P=0.002) had a gradually increased risk of hyperglycemia, when compared to those without family history of diabetes/no obesity. The risk of hyperglycemia was the highest in the subgroup with family history of diabetes/obesity (all P<0.05). Conclusions In the Nanjing population, a family history of diabetes and coexistent obesity may increase the risk of hyperglycemia, suggesting that weight control is conducive to the prevention of hyperglycemia among the population with family history of diabetes.