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OBJECTIVES: Serial evaluations of lactate concentration may be more useful in predicting outcomes in patients with out-of-hospital cardiac arrest (OHCA) than a single measurement. This study aimed to evaluate the impact of lactate clearance (LC) on clinical and neurologic outcomes in patients with OHCA who underwent extracorporeal cardiopulmonary resuscitation (ECPR). DESIGN: Retrospective multicenter observational study. SETTING: Patients with OHCA receiving ECPR at 36 hospitals in Japan between January 1, 2013, and December 31, 2018. PATIENTS: This study evaluated 1227 patients, with lactateinitial assessed upon emergency department admission and lactatesecond measured subsequently. To adjust for the disparity in the time between lactate measurements, the modified 6-hour LC was defined as follows: ([lactateinitial--lactatesecond]/lactateinitial) x 100 x (6/the duration between the initial and second measurements [hr]). The patients were divided into four groups according to the modified 6-hour LC with an equivalent number of patients among LC quartiles: Q1 (LC < 18.8), Q2 (18.8 < LC < 59.9), Q3 (60.0 < LC < 101.2), and Q4 (101.2 < LC). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 30-day survival rates increased as the 6-hour LC increased (Q1, 21.2%; Q2, 36.8%; Q3, 41.4%; Q4, 53.6%; p for trend < 0.001). In the multivariate analysis, the modified 6-hour LC was significantly associated with a 30-day survival rate (adjusted odds ratio [AOR], 1.003; 95% CI, 1.001-1.005; p < 0.001) and favorable neurologic outcome (AOR, 1.002; 95% CI, 1.000-1.004; p = 0.027). CONCLUSIONS: In patients with OHCA who underwent ECPR, an increase in the modified 6-hour LC was associated with favorable clinical and neurologic outcome. Thus, LC can be a criterion to assess whether ECPR should be continued. [ABSTRACT FROM AUTHOR]