The aim of this study was to compare the effects of Mediterranean-type diet (MD), high-fat diet (HFD), and red wine supplementation on plasma concentration of emergent haemostatic cardiovascular risk factors (HCVRF) and on variables of primary haemostasis (bleeding time, plasma von Willebrand factor and platelet aggregation/secretion). In a controlled prospective intervention study, two groups (21 healthy males each) received either MD or HFD during 90 days. Between days 30-60, both diets were supplemented with 240 ml/ day of red wine. After adjusting by baseline values, MD was associated with: lower plasma fibrinogen (p =0.03), factor VIIc (p=0.034) and factor VIIIc (p=0.0057); higher levels of protein S (p=0.013); longer bleeding time (p=0.017); and marginal increases in platelet serotonin aggregation and secretion after stimulation with epinephrine. Red wine supplementation, in both diets, resulted in decreased plasma fibrinogen (p=0.001) and factor VIIc (p=0.05), and in increased t-PA (p=0.01) and PAI-1 (p=0.0003). The effects of wine on antithrombin III (p=0.01) were divergent: there was a decrease in the HFD group but it increased slightly in the MD group. No effects of diet or wine were detected in plasma protein C, C-reactive protein or von Willebrand factor. BT did not change significantly with wine supplementation. Wine intake resulted in a significant increase in ex vivo platelet aggregation and secretion after stimulation with collagen (1 and 2 microg/ml, p < or = 0.01). MD and moderate consumption of red wine have complementary, mostly beneficial effects on haemostatic CV risk factors. The longer BT in individuals on MD, obtained independently of red wine, denotes less interaction of platelets with the vascular wall, which could be beneficial from the point of view of CV risk.