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Previous studies on the association between hs-CRP and incident type 2 diabetes among African Americans have been inconclusive. We examined the association between hs-CRP and incident diabetes in a large African American cohort (Jackson Heart Study).hs-CRP was measured in 3,340 participants. Incident diabetes was defined by fasting glucose ≥126 mg/dL, physician diagnosis, use of diabetes drugs, or A1C ≥6.5% (48 mmol/mol) at follow-up. Cox regression was used to estimate hazard ratios (HRs) for incident diabetes, adjusting for age, sex, education, diabetes family history, alcohol, HDL, triglycerides, hypertension status, hypertension medications, physical activity, BMI, HOMA-insulin resistance (HOMAIR), and waist circumference.Participants (63% women) were aged 53.3 ± 12.5 years. During a median follow-up of 7.5 years, 17.4% developed diabetes (23.1/1,000 person-years, 95% CI 21.3–25.1). After adjustment, the HR (hs-CRP third vs. first tertile) was 1.64 (95% CI 1.26–2.13). In separate models, further adjustment for BMI and waist circumference attenuated this association (HR 1.28 [95% CI 0.97–1.69] and 1.35 [95% CI 1.03–1.78, P < 0.05 for trend], respectively). Upon adding HOMAIR in the models, the association was no longer significant. In adjusted HOMAIR-stratified analysis, the hs-CRP–diabetes association appeared stronger in participants with HOMAIR <3.0 compared with HOMAIR ≥3.0 (P < 0.0001 for interaction). The association was also stronger among nonobese participants, although not significant when adjusted for HOMAIR.Low-grade inflammation, as measured by hs-CRP level, may have an important role in the development of diabetes among African Americans with a lesser degree of insulin resistance.