Background There is increasing evidence of an association between social relationships and morbidity in general, and cardiovascular disease in particular. However, recent syntheses of the evidence raise two important questions: is it the perceived quality or the more objective quantity of relationships that matters most; and what are the implications of changes in relationships over time? In this study, we investigate the cumulative effects of loneliness and social isolation on incident cardiovascular disease. Design A secondary analysis of prospective follow-up data from the English Longitudinal Study of Ageing (ELSA). Methods To assess the association between social isolation or loneliness and incident cardiovascular disease, lagged values of exposure to loneliness and isolation were treated as time-varying variables in discrete time survival models controlling for potential confounders and established cardiovascular disease risk factors. Results A total of 5397 men and women aged over 50 years were followed up for new fatal and non-fatal diagnoses of heart disease and stroke between 2004 and 2010. Over a mean follow-up period of 5.4 years, 571 new cardiovascular events were recorded. We found that loneliness was associated with an increased risk of cardiovascular disease (odds ratio 1.27, 95% confidence interval 1.01–1.57). Social isolation, meanwhile, was not associated with disease incidence. There was no evidence of a cumulative effect over time of social relationships on cardiovascular disease risk. Conclusions Loneliness is associated with an increased risk of developing coronary heart disease and stroke, independently of traditional cardiovascular disease risk factors. Our findings suggest that primary prevention strategies targeting loneliness could help to prevent cardiovascular disease.