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Rate of lactate change is associated with in-hospital mortality in post-cardiac arrest patients. This association has not been validated in a prospective multicenter study. The objective of the current study was to determine the association between percent lactate change and outcomes in post-cardiac arrest patients.Four-center prospective observational study conducted from June 2011 to March 2012.The National Post-Arrest Research Consortium is a clinical research network conducting research in post-cardiac arrest care. The network consists of four urban tertiary care teaching hospitals.Inclusion criteria consisted of adult out-of-hospital non-traumatic cardiac arrest patients who were comatose after return of spontaneous circulation.None.The primary outcome was survival to hospital discharge, and secondary outcome was good neurologic outcome. We compared the absolute lactate levels and the differences in the percent lactate change over 24 hours between survivors and nonsurvivors and between subjects with good and bad neurologic outcomes. One hundred patients were analyzed. The median age was 63 years (interquartile range, 50–75) and 40% were female. Ninety-seven percent received therapeutic hypothermia, and overall survival was 46%. Survivors and patients with good neurologic outcome had lower lactate levels at 0, 12, and 24 hours (p< 0.01). In adjusted models, percent lactate decrease at 12 hours was greater in survivors (odds ratio, 2.2; 95% CI, 1.1–6.2) and in those with good neurologic outcome (odds ratio, 2.2; 95% CI, 1.1–4.4).Lower lactate levels at 0, 12, and 24 hours and greater percent decrease in lactate over the first 12 hours post cardiac arrest are associated with survival and good neurologic outcome.