It remains unclear how coagulation and anticoagulant factors influence global coagulation assays such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). We measured PT, aPTT, coagulation factor and protein levels, and TGA parameters (lag time, endogenous thrombin potential [ETP], and peak thrombin) in 252 apparently healthy adults. Vitamin K-dependent coagulation and anticoagulant factors were significantly correlated with blood lipids. PT was determined by factor (F) V and FVII; aPTT was dependent on antithrombin, protein C, FVIII, and FXII. Lag time was mainly determined by FVII, FXII, and protein S and peak thrombin by FVIII and FIX. Antithrombin (for ETP and lag time) and protein S (for lag time) contributed significantly to TGA inhibition. This knowledge about determinants of global coagulation assays may help interpret the results of coagulation assays and contribute to the future development of diagnostic tools. The synchronized plasma levels of vitamin K-dependent proteins with opposite functionalities may compensate a propensity to hyper- or hypocoagulability in a normal population.