This study aims to evaluate the prevalence of patients with systemic sclerosis (SSc) in Split-Dalmatia County in Southern Croatia. Patients were recruited from the medical records of University Hospital Split. Our Department of Rheumatology and Clinical Immunology is the only tertiary referral center for the Split-Dalmatia County, which has a population of 313,365 inhabitants aged over 18 years. Diagnoses were verified by medical record review. Cases of localized scleroderma (morphea and linear disease) were excluded. All patients were re-evaluated by the American College of Rheumatology (ACR) criteria for the classification of systemic sclerosis. Prevalence of SSc in Split-Dalmatia County was estimated at 15.6 cases among 100,000 adults (95%CI 11.8-19.4). The prevalence of SSc in Split-Dalmatia County in Southern Croatia according only to the ACR criteria is higher than in other European countries. These data should facilitate research regarding the role of geographic and environmental factors for this disease in comparison populations.