We conducted a prospective, observational study to assess the prognostic value of hemostasis-related parameters in unselected ICU patients. We collected baseline characteristics from 497 consecutive unselected medical and trauma patients during their ICU stay. Each hemostasis-related parameter was analyzed alone or combined with APACHE II scores for any association with ICU mortality by calculating the under the curve (AUC) of the ROC curve, the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices. Of all hemostasis-related indicators examined, the AUC for fibrin degradation products (FDPs) was less than that for APACHE II scores, but larger than that for disseminated intravascular coagulation (DIC) scores. The prediction power of FDPs is relatively low. Multiple regression analysis revealed that FDPs and APACHE II scores significantly predicted primary outcome. The combined use of FDPs level and APACHE II scores generated an NRI of 9.94% and an IDI of 3.54%. In conclusion, FDP is the best independent indicator of ICU mortality among all hemostasis-related indicators examined. The use of FDP level and APACHE II scores in parallel significantly improves the ability to predict ICU mortality, suggesting the application of these parameters could be used to improve patient care and management in the ICU.