Introduction Genistein is an isoflavone phytoestrogen derived from the soybean which acts as natural selective estrogen receptor modulator. Various studies have pointed out its cardioprotective role. The aim of the study was to evaluate the haemostatic effects of genistein in postmenopausal women. Material and methods In this double-blind placebo-controlled trial we enrolled 104 healthy postmenopausal women with osteopenia. 53 patients (mean age 54.9 ± 4.2 yr; BMI 23.4 ± 3.2 Kg/m2) received genistein (54 mg/day) and 51 patients (mean age 55.4 ± 4.3 yr; BMI 23.6 ± 3.6 Kg/m2) received an identical placebo-tablet. Both groups received a calcium and vitamin D supplement. Plasma levels of D-dimer (DD), plasminogen activator inhibitor-1 (PAI-1) and prothrombin fragment 1 + 2 (F1 + 2) were measured at baseline and after 6 and 12 months of treatment. Results Baseline characteristics of the two groups were similar. Compared with placebo, genistein decreased significantly DD (p Conclusion The results of our study do not confirm effects of genistein on activation of the haemostatic system, but on the contrary the significant decrease of DD could indicate a possible cardioprotective role of genistein in postmenopausal women.