Background: Plasminogen activator inhibitor type 1 (PAI-1) plays a key role in fibrinolytic activity, which is important for thrombotic cardiovascular events. It has been suggested that moderate alcohol consumption may protect against coronary heart disease and ischemic stroke. However, little is known about the effects of moderate doses of alcohol on PAI-1. Methods and Results: We assessed the association between different levels of alcohol consumption and PAI-1 among 1862 participants of the National Heart, Lung, and Blood Institute Family Heart Study. We fitted a regression model, adjusting for anthropometric, metabolic, and lifestyle factors. Individuals in the highest alcohol intake category were leaner, had higher high-density lipoprotein cholesterol levels, smoked more cigarettes, and consumed less dietary fiber compared with never-drinkers. For drinking categories of never-drinkers, ex-drinkers, and current drinkers of 0.1 to 1.4, 1.5 to 4.9, 5.0 to 14.9, and ≥15 g/d of alcohol, multivariate adjusted geometric mean PAI-1 levels among women were 10.77, 9.41, 9.99, 11.21, 11.28, and 16.40 ng/mL, respectively. With similar categories except the top category divided into 15.0 to 29.9 and ≥30 g/d, PAI-1 levels among men were 18.43, 15.77, 15.19, 16.20, 17.27, 24.02, and 29.46 ng/mL, respectively. Conclusions: These results show that alcohol consumption up to 14.9 g/d is not associated with increased PAI-1, whereas the findings suggest increased PAI-1 with greater alcohol intake.