Clusterin has been demonstrated to be one of the anti-inflammatory and anti-apoptotic factors, suggesting the potential to be involved in the development of systemic sclerosis (SSc). The aim of this study is to determine serum clusterin levels and their clinical associations in patients with SSc. Serum clusterin levels were examined by enzyme-linked immunosorbent assay in 61 SSc patients and 24 healthy individuals. Serum clusterin levels were significantly elevated in SSc patients compared with healthy individuals (P < 0.001). Among SSc patients, there were no differences in serum clusterin levels between those with limited cutaneous SSc (n = 30) and those with diffuse cutaneous SSc (n = 31). SSc patients with raised clusterin levels had digital ulcers and pulmonary arterial hypertension less often than those with normal clusterin levels. The results show that the serum clusterin levels were increased in patients with SSc, and associated with a lower frequency of digital ulcers and pulmonary arterial hypertension. Clusterin could be a protective factor against the development of digital ulcers and pulmonary arterial hypertension in this disease and as such would be a possible therapeutic target.