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Background: We studied the prognostic ability of serum ubiquitin C‐terminal hydrolase L1 (UCH‐L1) after out‐of‐hospital cardiac arrest (OHCA), compared to that of neuron‐specific enolase (NSE). Methods: In this post‐hoc analysis of the FINNRESUSCI study, we measured serum concentrations of UCH‐L1 in 249 OHCA patients treated in 21 Finnish intensive care units in 2010–2011. We evaluated the ability of UCH‐L1 to predict unfavourable outcome at 12 months (defined as cerebral performance category 3–5) by assessing the area under the receiver operating characteristic curve (AUROC), in comparison with NSE. Results: The concentrations of UCH‐L1 were higher in patients with unfavourable outcome than for those with favourable outcome: median concentration 10.8 ng/mL (interquartile range, 7.5–18.5 ng/mL) versus 7.8 ng/mL (5.9–11.8 ng/mL) at 24 h (p <.001), and 16.2 ng/mL (12.2–27.7 ng/mL) versus 11.5 ng/mL (9.0–17.2 ng/mL) (p <.001) at 48 h after OHCA. For UCH‐L1 as a 12‐month outcome predictor, the AUROC was 0.66 (95% confidence interval, 0.60–0.73) at 24 h and 0.66 (0.59–0.74) at 48 h. For NSE, the AUROC was 0.66 (0.59–0.73) at 24 h and 0.72 (0.65–0.80) at 48 h. The prognostic ability of UCH‐L1 was not different from that of NSE at 24 h (p =.82) and at 48 h (p =.23). Conclusion: Concentrations of UCH‐L1 in serum were higher in patients with unfavourable outcome than in those with favourable outcome. However, the ability of UCH‐L1 to predict unfavourable outcome after OHCA was only moderate and not superior to that of NSE. [ABSTRACT FROM AUTHOR]