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This study aimed to compare the prognostic value of lactate level and lactate clearance at 6 hours after septic shock recognition. And, we performed it to determine lactate kinetics in the Sepsis-3 defined septic shock.This retrospective study was performed from a prospective septic shock registry.This study was performed at single urban tertiary center. And, all patients were treated with protocol-driven resuscitation bundle therapy between 2010 and 2016.We included septic shock patients who met the Sepsis-3 definition, which involves lactate levels greater than or equal to 2 mmol/L and vasopressor use.Serum lactate levels were measured at initial and 6 hours from septic shock recognition.Lactate clearance was calculated as ([initial lactate – 6-hr lactate]/initial lactate) × 100. The prognostic value of measured lactate levels and lactate clearance for 28-day mortality was analyzed and compared with that of subsequent lactate levels greater than or equal to 2 mmol/L, greater than or equal to 3 mmol/L, and greater than or equal to 4 mmol/L and less than 10%, less than 20%, and less than 30% lactate clearance. A total of 1,060 septic shock patients by Sepsis-3, 265 patients died (28-d mortality: 25%). In survivor, groups had lower median 6-hour lactate level and higher lactate clearance than nonsurvivors (2.5 vs 4.6 mmol/L and 35.4% vs 14.8%; p < 0.01). Both lactate and lactate clearance were associated with mortality after adjusting for confounders (odd ratio, 1.27 [95% CI, 1.21–1.34] and 0.992 [95% CI, 0.989–0.995]), but lactate had a significantly higher prognostic value than lactate clearance (area under the curve, 0.70 vs 0.65; p < 0.01). The prognostic value of subsequent lactate levels (≥ 2, ≥ 3, and ≥ 4 mmol/L) and lactate clearances (< 10%, < 20%, and < 30%) was not significantly differed. However, lactate levels of greater than or equal to 2 mmol/L had the greatest sensitivity (85.3%).Our findings indicate lactate and lactate clearance are both useful targets in patients with septic shock defined by Sepsis-3. Serum lactate level at 6-hour can be an easier and more effective tool for prognosis of septic shock patients who were treated with protocol-driven resuscitation bundle therapy.