Systemic sclerosis (SSc) is a connective tissue disorder of unknown etiology characterized by fibrosis and vascular obliteration in the skin, gastrointestinal tract, lungs, and heart. Our aim was to investigate the autoantibody profile in patients with esophageal involvement of SSc and to describe the relationship between the autoantibody profile and organ involvement in SSc. We studied 47 SSc patients, all with esophageal involvement shown on esophageal manometry. The patients were separated into three groups based on the absence or presence of ANA, Scl70, and ACA. In this study ANA and Scl70 were present more frequently than ACA in patients with esophageal involvement of SSc. Pulmonary involvement and heart involvement were seen more in Scl70-positive and ACA-positive patients, respectively. We conclude that in patients with SSc, closer follow-up with autoantibody profile may enable early diagnosis of specific organ involvement and treatment of debilitating symptoms, with avoidance of potential life-threatening complications.