Object: We aimed to investigate the clinical factors affecting the therapeutic efficacy of empagliflozin in subjects with type 2 diabetes mellitus (T2DM). Methods: We enrolled 507 T2DM subjects who aged 20~80 years and had been prescribed empagliflozin 10 or 25mg as add-on therapy for > 90 consecutive days. Changes in HbA1c from baseline (%) in subgroups were assessed. Results: The younger subjects (≤ 50 years) had a better glycemic response than did those aged 51-60 years (1.08 ± 0.12 vs. 0.73 ± 0.09, P = 0.039) and those aged > 60 (1.08 ± 0.12 vs. 0.44 ± 0.08, P < 0.001). No significant difference by BMI was observed (P = 0.685). Subjects with the highest baseline HbA1c ( > 9%) had a better response than did those with baseline HbA1c ≤ 7.5% (1.79 ± 0.13 vs. 0.50 ± 0.06, P < 0.001) and 7.5~9% (1.79 ± 0.13 vs. 0.06 ± 0.05, P < 0.001). Subjects with an eGFR > 100 mL/min/1.73 ㎡ demonstrated a better response than did those with an eGFR ≤ 90 mL/min/1.73㎡ (1.05 ± 0.10 vs. 0.48 ± 0.09, P < 0.001) and 90~100 mL/min/1.73㎡ (1.05 ± 0.10 vs. 0.66 ± 0.90, P = 0.022). By multivariate linear regression analysis, shorter T2DM duration (β = -0.028; p < 0.001), higher baseline HbA1c (β = 0.573; p < 0.001) and higher eGFR (β = 0.014; p < 0.001) demonstrated a positive association with the HbA1c reduction after adjusting for age, gender, T2DM duration, baseline HbA1c and eGFR. Conclusion: A glucose-lowering effect of empagliflozin is more evident in T2DM patients with higher baseline HbA1c and better renal function.