Vascular disease is universal in patients with systemic sclerosis (SSc), but there is a wide variability in its severity. It is clear that there is an early insult to the microvasculature, followed-up by on-going chronic process. This results in profound vascular damage in a subset of patients who develop severe events such as digital loss and pulmonary arterial hypertension. Although there is abundant evidence of vascular perturbation from studies of peripheral blood in SSc, there are few data about the ability to use these biomarkers to predict vascular outcomes. This paper examines the possibility of using circulating biomarkers to assess vascular disease activity and to predict severe vascular events among patients with SSc.