There is strong and consistent evidence across numerous studies that social isolation or lack of social support is an independent risk factor for incident coronary heart disease. However, the impact of social isolation or lack of social support on the progression of coronary atherosclerosis in women has not been well documented. Among 292 women, aged 30-65 years, consecutively hospitalized with acute myocardial infarction or unstable angina between 1991 and 1994 enrolled in the female coronary risk study, 102 women were available to study disease progression over an average of 3.2 years. Three aspects of social support were studied: emotional support, social integration, and interpersonal social relations. Quantitative coronary angiography was performed 3-6 months following index hospitalization and repeated 3 years later. Progression of coronary atherosclerosis was evaluated as the change in mean luminal diameter from first to second measurements of 10 pre-defined coronary segments. Mixed model ANOVA was used to analyze the impact of social support on progression of coronary atherosclerosis. Significantly greater coronary atherosclerosis progression was found among women who lacked emotional support (mean coronary artery luminal diameter narrowing by 0.15 mm), with social isolation (0.14 mm), and lack of interpersonal social relations (0.13 mm), whereas women with high levels of support progressed less. It was 0.05 mm in women with high levels of emotional support, 0.07 mm for socially integrated women, and 0.04 mm in women with adequate interpersonal social relations. These associations were independent of conventional clinical and lifestyle factors such as age, smoking history, body mass index, menopausal status, and diagnosis of index event of acute myocardial infarction. The results of our study suggest that lack of emotional support, social isolation, and lack of interpersonal social relations are important risk factors for accelerated progression of coronary atherosclerosis in middle-aged women.