Objective To evaluate health‐related quality of life (HRQOL) in patients with systemic sclerosis (SSc) using the Short Form 36 (SF‐36) and to correlate SF‐36 scores with clinical and biologic markers. Methods The SF‐36 was administered to 24 controls and 24 SSc patients. SSc patients also were evaluated for subset (limited SSc [lSSc] and diffuse SSc [dSSc]), age, disease duration, angiotensin‐converting enzyme (ACE) levels, autoantibodies, and skin and internal organ involvement. Results The physical summary score (PSS) was lower in SSc patients than in controls (P < 0.05), whereas the mental summary score (MSS) was higher in dSSc than in lSSc patients (P < 0.05). Five of 8 single SF‐36 domain scores were lower in SSc patients than in controls (P < 0.05). Vitality was higher in dSSc than in controls (P < 0.001). In SSc, elder age correlated with lower PSS; low ACE levels and high skin score correlated with higher general mental health and role limitations due to physical problems, respectively (P < 0.05). Patients with heart involvement had higher scores in general health perceptions (P < 0.05). Conclusion The SF‐36 shows that HRQOL is impaired in patients with SSc. Higher scores in MSS and vitality in patients with dSSc and correlations of high SF‐36 scores with specific organ involvement suggest that SSc patients with severe disease are more able to cope with HRQOL modification.