The American Diabetes Association now recommends hemoglobin A(1c) (HbA(1c)) screening for the diagnosis of diabetes. It has been reported that HbA(1c) levels underestimate glycemic levels in HIV-infected persons. We examined the performance of HbA(1c) as a screening test for diabetes in a group of HIV-infected people without diabetes. We conducted a retrospective cross-sectional cohort study among HIV-infected patients determining the sensitivity and specificity of HbA(1c) as a screening test compared to fasting blood glucose (FBG). The effect of treatment regimen on the relationship between HbA(1c) and FBG was assessed by multiple linear regressions. Twenty-two of the 395 patients included in the study were newly diagnosed with diabetes based on FBG≥126 mg/dL. Using a cutoff of HbA(1c)≥6.5%, HbA(1c) had a sensitivity of 40.9% and specificity of 97.5% for identification of incident diabetes. At an HbA(1c) level of 5.8% the product of sensitivity and specificity was maximized, with values of 88.8% and 77.5% respectively. Higher mean cell volume (MCV) values (p=0.02) and current use of a non-nucleoside reverse transcriptase inhibitors (NNRTIs; p=0.02) significantly increased the slope, while PI use significantly decreased the slope (p<0.001), of the linear regression of HbA(1c) compared to FBG. Tenofovir use did not significantly alter the slope or y-intercept of the line. Among HIV-infected nondiabetic patients, HbA(1c) is insensitive, although highly specific for diagnosing diabetes. Current antiretroviral (ART) use has significant and variable influence on the relationship between HbA(1c) and FBG. The use of HbA(1c) in conjunction with FBG may be the best modality to screen for diabetes.