This study was designed to investigate the pharmacokinetics of an innovative film-coated warfarin sodium tablet and to compare it with the marketed sugar-coated warfarin sodium tablet in humans. A single-dose, open-label, randomized, two-way crossover study was performed in 24 healthy Chinese male volunteers. They were administered 2.5 mg of innovative film-coated warfarin sodium tablets or the marketed sugar-coated warfarin sodium tablets. Blood samples were collected at different time points after dosing for investigation of the pharmacokinetics of warfarin in human plasma. A sensitive liquid chromatography mass spectrometry method was established to determine warfarin in plasma. Drug and Statistics 2.1.1 was applied to calculate the pharmacokinetics parameters. The main pharmacokinetic parameters for film-coated and sugar-coated warfarin were the following: t½ , 103.5 ± 18.8 and 105.8 ± 21.3 hours; Tmax , 0.7 ± 0.5 and 1.3 ± 0.8 hours; Cmax , 347.8 ± 74.8 and 322.9 ± 75.7 ng/mL; AUC0∼360 , 16,024.2 ± 3713.9 and 15,586.6 ± 3477.0ng·mL-1 ·h; AUC0∼∞ , 17,335.7 ± 4089.1 and 16,912.0 ± 3911.2 ng·mL-1 ·h, respectively. The human pharmacokinetics of film-coated and sugar-coated warfarin were slightly different. The oral absorption and bioavailability of innovative film-coated warfarin were slightly higher than those of the sugar-coated warfarin. This study is vital to clinical usage of warfarin not only because of the pharmacokinetic parameters of the 2 pharmaceutical dosage forms of warfarin but also to obtain data on the prevalence of CYP2C9 and VKORC1 genes and their influence on the concentration of warfarin.