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Background: This study assessed the association between the initial Acute Physiology and Chronic Health Evaluation (APACHE) II score and good neurological outcome in comatose survivors of out-of-hospital cardiac arrest who received targeted temperature management (TTM). Methods: Data from survivors of cardiac arrest who received TTM between January 2011 and June 2016 were retrospectively analyzed. The initial APACHE II score was determined using the data immediately collected after return of spontaneous circulation rather than within 24 hours after being admitted to the intensive care unit. Good neurological outcome, defined as Cerebral Performance Category 1 or 2 on day 28, was the primary outcome of this study. Results: Among 143 survivors of cardiac arrest who received TTM, 62 (43.4%) survived, and 34 (23.8%) exhibited good neurological outcome on day 28. The initial APACHE II score was significantly lower in the patients with good neurological outcome than in those with poor neurological outcome (23.71 ± 4.39 vs. 27.62 ± 6.16, P = 0.001). The predictive ability of the initial APACHE II score for good neurological outcome, assessed using the area under the receiver operating characteristic curve, was 0.697 (95% confidence interval [CI], 0.599 to 0.795; P = 0.001). The initial APACHE II score was associated with good neurological outcome after adjusting for confounders (odds ratio, 0.878; 95% CI, 0.792 to 0.974; P = 0.014). Conclusions: In the present study, the APACHE II score calculated in the immediate post-cardiac arrest period was associated with good neurological outcome. The initial APACHE II score might be useful for early identification of good neurological outcome.