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We investigated the relationship between lactate clearance and outcome in patients surviving the first 48 hours after cardiac arrest. We conducted the study in the emergency department of an urban tertiary care hospital. We analyzed the data for all 48-hour survivors after successful resuscitation from cardiac arrest during a 10-year period. Serial lactate measurements, demographic data, and key cardiac arrest data were correlated to survival and best neurologic outcome within 6 months after cardiac arrest. Parameters showing significant results in univariate analysis were tested for significance in a logistic regression model. Of 1502 screened patients, 394 were analyzed. Survivors (n = 194, 49%) had lower lactate levels on admission (median, 7.8 [interquartile range, 5.4-10.8] vs 9 [6.6-11.9] mmol/L), after 24 hours (1.4 [1-2.5] vs 1.7 [1.1-3] mmol/L), and after 48 hours (1.2 [0.9-1.6] vs 1.5 [1.1-2.3] mmol/L). Patients with favorable neurologic outcome (n = 186, 47%) showed lower levels on admission (7.6 [5.4-10.3] vs 9.2 [6.7-12.1] mmol/L) and after 48 hours (1.2 [0.9-1.6] vs 1.5 [1-2.2] mmol/L). In multivariate analysis, lactate levels at 48 hours were an independent predictor for mortality (odds ratio [OR]: 1.49 increase per mmol/L, 95% confidence interval [CI]: 1.17-1.89) and unfavorable neurologic outcome (OR: 1.28 increase per mmol/L, 95% CI: 1.08-1.51). Lactate levels higher than 2 mmol/L after 48 hours predicted mortality with a specificity of 86% and poor neurologic outcome with a specificity of 87%. Sensitivity for both end points was 31%. Lactate at 48 hours after cardiac arrest is an independent predictor of mortality and unfavorable neurologic outcome. Persisting hyperlactatemia over 48 hours predicts a poor prognosis.