Hyperglycemia, dyslipidemia and hyperhomocysteinemia are associated with both adult cardiovascular disease (CVD) and having a child with a congenital heart disease (CHD). We investigated associations between CVD in grandparents and the risk of CHD in grandchildren. In a case–control family study, we obtained detailed questionnaire information on CVD and CHD in 247 families with a CHD child and 203 families without a CHD child. Grandparents with CVD or intermittent claudication (IC) were significantly associated with an increased risk for CHD in grandchildren [OR 1.39 (95% CI 1.03–1.89) and OR 2.77 (95% CI 1.02–7.56), respectively]. The risk of CHD grandchildren was particularly increased in paternal grandfathers with CVD [OR 1.85 (95% CI 1.01–3.37)]. Overall, having a grandparent with CVD increased the risk for CHD in the grandchild by 1.65 (95% CI 1.12–2.41). After adjustment for potential maternal confounders, this risk was 1.44 (95% CI 0.94–2.21). Having two or more grandparents with CVD was associated with an approximately threefold risk for CHD grandchildren [OR adjusted 2.72 (95% CI 1.08–6.89)]. Our data suggest that CVD and IC in grandparents are associated with an increased risk of having a CHD grandchild. These first findings may be explained by shared causality of derangements in metabolic pathways and are in line with the fetal origins of health and disease.