The aim of this study was to evaluate health-related quality of life (HR-QOL) in patients with systemic sclerosis (SSc), to compare it with that of patients with rheumatoid arthritis (RA), and to correlate it with other parameters. HR-QOL was evaluated by the Short Form 36 (SF-36), SSc disease activity and severity by preliminary indexes recently proposed, disability by the Health Assessment Questionnaire (HAQ), and depressive symptoms by the Beck Depression Inventory. HR-QOL perception was not statistically different in patients with SSc and RA, except that patients with diffuse cutaneous involvement had worse scores in the general health and mental health dimensions than patients with RA (p=0.03). Compared with RA, patients with SSc tended to perceive less bodily pain (p=0.06) and have less disability (p=0.04) but to report higher depressive symptom scores (p=0.05). SSc patients' HR-QOL was associated with some disease severity scales (general, kidney and, less significantly, heart), but it was poorly correlated with the other evaluated disease activity and severity indexes. A strong correlation with disability and with depressive symptoms was observed. In conclusion, patients with SSc perceived a reduced HR-QOL similar to that of patients with RA. SF-36 may provide useful information in their evaluation.