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To determine whether early lactate reduction is associated with improved survival and good neurologic outcome in patients with out-of-hospital cardiac arrest.Ad hoc data analysis of a prospective, multicenter observational study.Out-of-hospital cardiac arrest patients at 67 emergency hospitals in Kanto, Japan between January 2012 and March 2013.Adult patients with out-of-hospital cardiac arrest admitted to the hospital after successful resuscitation were identified.Blood lactate concentrations were measured at hospital admission and 6 h after hospital admission. Early lactate clearance was defined as the percent change in lactate level 6 h after a baseline measurement.The 543 patients (mean age, 65 ± 16 yr; 72.6% male) had a mean lactate clearance of 42.4% ± 53.7%. Overall 30-day survival and good neurologic outcome were 47.1% and 27.4%, respectively. The survival proportion increased with increasing lactate clearance (quartile 1, 29.4%; quartile 2, 42.6%; quartile 3, 51.5%; quartile 4, 65.2%; p < 0.001). Multivariate logistic regression analysis showed that lactate clearance quartile was an independent predictor of the 30-day survival and good neurologic outcome. In the Cox proportional hazards model, the frequency of mortality during 30 days was significantly higher for patients with lactate clearance in quartile 1 (hazard ratio, 3.12; 95% CI, 2.14–4.53), quartile 2 (hazard ratio, 2.13; 95% CI, 1.46–3.11), and quartile 3 (hazard ratio, 1.49; 95% CI, 1.01–2.19) than those with lactate clearance in quartile 4. Furthermore, multivariate logistic regression analysis revealed that lactate clearance was a significant predictor of good neurologic outcome at 30 days after hospital admission.Effective lactate reduction over the first 6 hours of postcardiac arrest care was associated with survival and good neurologic outcome independently of the initial lactate level.