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Dysglycemia and glycemic variability are associated with poor outcomes in critically ill patients. Targeted temperature management alters blood glucose homeostasis. We investigated the association between blood glucose concentrations and glycemic variability and the neurologic outcomes of patients randomized to targeted temperature management at 33°C or 36°C after cardiac arrest.Post hoc analysis of the multicenter TTM-trial. Primary outcome of this analysis was neurologic outcome after 6 months, referred to as “Cerebral Performance Category.”Thirty-six sites in Europe and Australia.All 939 patients with out-of-hospital cardiac arrest of presumed cardiac cause that had been included in the TTM-trial.Targeted temperature management at 33°C or 36°C.Nonparametric tests as well as multiple logistic regression and mixed effects logistic regression models were used. Median glucose concentrations on hospital admission differed significantly between Cerebral Performance Category outcomes (p < 0.0001). Hyper- and hypoglycemia were associated with poor neurologic outcome (p = 0.001 and p = 0.054). In the multiple logistic regression models, the median glycemic level was an independent predictor of poor Cerebral Performance Category (Cerebral Performance Category, 3–5) with an odds ratio (OR) of 1.13 in the adjusted model (p = 0.008; 95% CI, 1.03–1.24). It was also a predictor in the mixed model, which served as a sensitivity analysis to adjust for the multiple time points. The proportion of hyperglycemia was higher in the 33°C group compared with the 36°C group.Higher blood glucose levels at admission and during the first 36 hours, and higher glycemic variability, were associated with poor neurologic outcome and death. More patients in the 33°C treatment arm had hyperglycemia.