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The benefit of a high level of high-density lipoprotein cholesterol (HDL-C) against coronary atherosclerosis risk after achieving optimal glycemic control (OGC) in diabetics remains uncertain. We aimed to evaluate the association between HDL-C and obstructive coronary artery disease (CAD) according to OGC status in diabetics. We analyzed 1,114 asymptomatic diabetics who underwent coronary computed tomographic angiography in a health examination. OGC was defined as hemoglobin A1C <7.0%. Obstructive CAD was defined as the presence of plaques with ≥50% stenosis. Patients with a high HDL-C level (≥40 mg/dL and ≥50 mg/dL in males and females, respectively) showed a lower prevalence of obstructive CAD than those with a low HDL-C level in the OGC group (8.9% vs. 14.4%; p = 0.046), but not in the non-OGC group (22.3% vs. 23.2%, p = 0.850). Multiple logistic regression models showed that the risk for obstructive CAD was lower in patients with a high HDL-C level than in those with a low HDL-C level in the OGC group (odds ratio: 0.584, 95% confidence interval: 0.343–0.995; p = 0.048), but not in the non-OGC group. In conclusion, it may be necessary to maintain a high HDL-C level to reduce the risk of obstructive CAD in asymptomatic diabetics after OGC is achieved. [ABSTRACT FROM AUTHOR]