The aim of this study is to assess the validity of combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) as screening tests for diabetes and impaired glucose tolerance (IGT) in high-risk subjects. A total of 2,298 subjects were included. All subjects underwent a 75-g oral glucose tolerance test (OGTT) and HbA1c measurement. Receiver operating characteristic curve (ROC curve) analysis was used to examine the sensitivity and specificity of FPG and HbA1c for detecting diabetes and IGT, which was defined according to the 1999 World Health Organization (WHO) criteria. (1) Based on the ROC curve, the optimal cut point of FPG related to diabetes diagnosed by OGTT was 6.1 mmol/l that was associated with a sensitivity and specificity of 81.5 and 81.0%, respectively; The optimal cut point of HbA1c related to diabetes diagnosed by OGTT was 6.1%, which was associated with a sensitivity and specificity of 81.0 and 81.0%, respectively; The screening model using FPG > or = 6.1 mmol/l or HbA1c > or = 6.1% had sensitivity of 96.5% for detecting undiagnosed diabetes; the screening model using FPG > or = 6.1 mmol/l and HbA1c > or = 6.1% had specificity of 96.3% for detecting undiagnosed diabetes. (2) Based on the ROC curve, the optimal cut point of FPG related to IGT diagnosed by OGTT was 5.6 mmol/l that was associated with a sensitivity and specificity of 64.1 and 65.4%, respectively; The optimal cut point of HbA1c related to IGT diagnosed by OGTT was 5.6%, which was associated with a sensitivity and specificity of 66.2 and 51.0%, respectively; The screening model using FPG > or = 5.6 mmol/l or HbA1c > or = 5.6% had sensitivity of 87.9% for detecting undiagnosed IGT; The screening model using FPG > or = 5.6 mmol/l and HbA1c > or = 5.6% had specificity of 82.4% for detecting undiagnosed IGT. Compared with FPG or HbA1c alone, the simultaneous measurement of FPG and HbA1c (FPG and/or HbA1C) might be a more sensitive and specific screening tool for identifying high-risk individuals with diabetes and IGT at an early stage.