Thrombin has become an important target for designing antithrombotic drugs in the recent years. Thus, we have undertaken a QSAR analysis aimed at individuating the physicochemical properties governing the inhibitory activity of such compounds. The QSAR equations for ten series of derivatives have been calculated and discussed. The series studied are all those that we found in the literature suitable for a QSAR study. The equations we obtained show that the main physicochemical properties affecting the inhibitory activity are almost the same for all the series and can be individuated by the use of proper parameters. The conclusions of this analysis can be summarized as follows: a). hydrophobicity plays a critical role; b). steric factors are also significant but in some cases the collinearity between steric and hydrophobic parameters does not allow one to draw any final conclusion.