AIMS: Increasing attention has been paid to the potential metabolic benefits of ketone bodies, but the clinical relevance of ketone bodies in newly diagnosed type 2 diabetes mellitus (T2D) remains unclear. We investigated the clinical implications of ketone bodies at the time of diagnosis in patients with drug-naïve T2D. METHODS: Clinical data including serum β-hydroxybutyrate (βHB) levels, were collected from 369 patients with newly diagnosed drug-naïve T2D from 2017 to 2021. Subjects were categorized into four βHB groups based on the level of initial serum βHB. The associations of initial serum βHB and urinary ketone levels with glucometabolic indices were analyzed. RESULTS: Higher serum βHB group was associated with higher levels of glycemic parameters including glycated hemoglobin (HbA1c) with lower levels of indices for insulin secretory function at the point of initial diagnosis of T2D. Nevertheless, higher serum βHB group was an independent determinant of a greater relative improvement in HbA1c after 6 months of anti-diabetic treatment, regardless of the type of anti-diabetic drug. In addition, patients in higher serum βHB group were more likely to have well-controlled HbA1c levels (≤6.5%) after 6 months of anti-diabetic treatment. CONCLUSION: In patients with newly diagnosed T2D, a higher initial βHB level was a significant predictive marker of greater glycemic improvement after antidiabetic treatment, despite its associations with hyperglycemia and decreased insulin secretion at baseline.