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In patients with out-of-hospital cardiac arrest (OHCA), the probability of resuscitation is strongly influenced by the duration of cardiac arrest, which activates the blood coagulation–fibrinolysis system. Because plasma D-dimer levels reflect activity of blood coagulation and fibrinolysis, they should increase with the duration of cardiac arrest. We evaluated 222 consecutive non-traumatic witnessed OHCA patients who underwent measurement of plasma D-dimer levels on arrival in the emergency room. Return of spontaneous circulation was achieved in 138 patients (62%), but only 42 (19%) were alive 30 days post-OHCA. D-dimer levels were elevated in 217 patients (97.7%). There was a positive correlation between plasma D-dimer levels and duration of cardiac arrest in the 222 patients (r = 0.623, p < 0.001). When the cause of OHCA was limited to cardiovascular disease, the positive correlation between level of D-dimer and the duration of cardiac arrest (r = 0.776, p < 0.001) increased. D-dimer levels were significantly lower in survivors than in non-survivors [9.5 (1.4–17.5) vs 54.2 (34.2–74.3) μg/mL, p = 0.024]. Receiver operating characteristic curve analysis showed that a cutoff value of D-dimer ≤ 10 μg/L led to sensitivity (69.0%) and specificity (72.8%) for 30 day survival (area under curve 0.75). Multivariate logistic regression analysis showed that D-dimer ≤ 10 μg/ml was an independent predictor for 30 day survival (odds ratio 4.39, 95% confidence interval 1.41–13.70; p = 0.01). D-dimer level correlates with duration of cardiac arrest, especially in OHCA patients due to cardiovascular causes, and may help physicians assess the probability of survival in OHCA patients. [ABSTRACT FROM AUTHOR]