Moderate red wine consumption has been associated with decreased risk of coronary heart disease. Reduced plasma viscosity and fibrinogen levels have been launched as possible contributors to this risk reduction. The effect of moderate red wine consumption on plasma viscosity, however, has not been investigated in a prospective, randomized trial. We wanted to evaluate the effect of moderate red wine consumption on plasma viscosity, fibrinogen concentration and fibrinogen subfractions. Healthy, nonsmoking volunteers were assigned to consume one glass of red wine daily for 3 weeks in a prospective, randomized cross-over study. In the second 3-week period the volunteers abstained from alcohol use. The plasma viscosity, fibrinogen concentration and the distribution of the main fibrinogen subfractions were determined at inclusion, after wine drinking and after abstention. Plasma viscosity was reduced by 0.026 and 0.024 mPa.s in the two groups following wine intake (95% confidence interval, 0.009-0.043, P = 0.004; 95% confidence interval, 0.0083-0.039, P = 0.003). The decrease in plasma viscosity was maintained following 3 weeks of abstention. The fibrinogen concentration was reduced by 0.17 g/l following wine drinking in the group starting with abstention (95% confidence interval, 0.04-0.29, P = 0.01). The distribution of the fibrinogen subfractions remained unaltered. We conclude that a daily glass of red wine for 3 weeks significantly reduces plasma viscosity. Fibrinogen concentrations are also significantly reduced, when preceded by an abstention period. The decreased viscosity levels are maintained after 3 weeks of abstention, suggesting a sustained viscosity lowering effect of red wine.