The prognosis for patients with systemic sclerosis (SSc) has improved in the past three decades, with fewer patients succumbing to renal-crisis-related death. While pulmonary fibrosis and hypertension are currently the most frequent causes of death, there is evidence that cardiovascular disease will have an important role in the long-term prognosis of SSc in the future. Ischemia-reperfusion injury and endothelial dysfunction are cardinal features of SSc, and may predispose a patient to microvascular disease and atherosclerosis. In order to alleviate the cardiovascular burden in patients with SSc, it is important to detect endothelial dysfunction, microvascular flow disturbance and atherosclerosis. Noninvasive techniques that evaluate flow-mediated dilatation and arterial pulse waves (endothelial function measurements), microvascular blood flow (measurement of the microcirculation), carotid intima-media thickness and left ventricular hypertrophy (detection of atherosclerosis) are recommended. In addition, these measurements will facilitate trials of therapeutic strategies that, in addition to controlling conventional risk factors, prevent and treat cardiovascular disease in patients with SSc.