Introduction: Hyperglycemia has adverse outcomes in resuscitated patients who have experienced cardiac arrest. Therapeutic hypothermia has a neuroprotective effect in these patients and improves outcome. However, the optimal acute plasma glucose level for cardiac arrest patients in the therapeutic hypothermia era is still unclear. Hypothesis: We assessed the hypothesis that mild to moderately acute hyperglycemia is associated with improved neurological outcome in cardiac arrest patients treated with hypothermia. Methods: Between September 2003 and May 2011, comatose survivors of cardiac arrest, who were treated with mild hypothermia, were retrospectively enrolled in this study. Plasma glucose was measured after the indexed cardiac arrest. The study patients were divided into four groups according to plasma glucose levels: Q1 (<11.1 mmol/l), Q2 (11.2-14.5 mmol/l), Q3 (14.6-18.4 mmol/l), and Q4 (>18.5 mmol/l). Neurological outcomes were assessed by cerebral performance categories at discharge. Cox proportional regression analysis was used to estimate independent predictors of favorable neurological outcome and optimal acute plasma glucose levels. Results: Median age, rate of ventricular fibrillation, and median time interval from collapse to return of spontaneous circulation in Q1 (N = 36), Q2 (N = 38), Q3 (N = 37), and Q4 (N = 37) patients were 58, 55, 63, and 57 y (P = 0.42); 42%, 76%, 62%, and 54% (P = 0.02); and 40, 23, 33, and 41 min (P = 0.01), respectively. The rates of favorable neurological outcome in Q1 (N = 36), Q2 (N = 38), Q3 (N = 37), and Q4 (N = 37) patients were 25%, 66%, 43%, and 16%, respectively. Q1 [odds ratio (OR) 0.21; 95% confidence interval (CI), 0.05-0.78] and Q4 (OR, 0.14; 95%CI, 0.03-0.56) were significantly associated with an unfavorable neurological outcome after adjusting for baseline characteristics. Conclusions: Optimal acute plasma glucose levels for cardiac arrest patients treated with hypothermia ranged from 11.2-18.4 mmol/l, which was usually thought to be hyperglycemia.