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OBJECTIVE: To determine whether the relationship between average glucose (AG) levels and hemoglobin A1c (HbA1c) differs across racial/ethnic groups. RESEARCH DESIGN AND METHODS: We performed a prospective substudy of GRADE, a comparative effectiveness randomized trial conducted in 36 centers in the U.S. A total of 1,454 of the 5,047 participants in the GRADE cohort, including 534 non-Hispanic White (NHW), 389 non-Hispanic Black (NHB), and 327 Hispanic White patients and 204 patients of other racial/ethnic backgrounds, were included in the substudy. Continuous glucose monitoring (CGM) performed for 10 days was used to calculate AG10. Immediately after CGM, HbA1c and glycated albumin were measured. Fasting plasma glucose (FPG) and glucose area under the curve (AUC) were derived from a 75-g oral glucose tolerance test. RESULTS: The relationship between AG10 and HbA1c was significantly different for NHB compared with NHW patients and those of other racial/ethnic groups. HbA1c levels were 0.2–0.6 percentage points higher in NHB than in NHW patients for AG10 levels from 100 to 250 mg/dL. For an HbA1c of 7%, AG10 was 11 mg/dL higher for NHW than for NHB patients. Similar findings were observed across races for relationships of FPG and AUC with HbA1c and for glucose measurements with glycated albumin levels. Differences in the relationship between AG10 and HbA1c across racial groups remained after adjustments for any demographic or other differences between racial/ethnic subgroups. CONCLUSIONS: The relationship between several measures of glucose with HbA1c and glycated albumin consistently differed across races. These findings should be considered in setting treatment goals and diagnostic levels. [ABSTRACT FROM AUTHOR]