OBJECTIVE: Systemic sclerosis (SSc) often presents alongside other connective tissue disorders, termed "overlap syndrome." This study aimed to characterize SSc patients with overlap syndrome compared to those without it in a tertiary university hospital in Brazil. METHODS: A retrospective analysis of demographic, clinical, and laboratory data from 787 SSc patients was performed using electronic medical records. Patients were classified based on the 2013 ACR/EULAR criteria for SSc and additional criteria for systemic lupus erythematosus (SLE), idiopathic inflammatory myopathy (IIM), Sjogren syndrome (SjD), and rheumatoid arthritis (RA). Statistical analysis, including univariate and multivariate methods, identified factors associated with overlap syndrome. RESULTS: Ninety-one patients (11.6%) had overlap syndrome, mainly with SLE (29.7%), SjD (26.4%), RA (24.2%), or IIM (19.8%). Patients with overlap syndrome were younger, with an earlier age at onset (P=0.004) and at diagnosis (P=0.003). They presented a higher prevalence of limited SSc (trend
P=0.056), musculoskeletal symptoms (P<
0.001), neoplasias (P=0.027), and sicca symptoms (P<
0.001), associated with a lower frequency of pulmonary hypertension (P=0.048) and comorbidities such as diabetes mellitus (P=0.016) and dyslipidemia (P=0.019). A higher prevalence of anti-Ro (P=0.007) and a lower prevalence of anti-Scl70 antibodies (P=0.007) were also observed. Regarding medications, patients with overlap were more frequently prescribed prednisone (P<
0.001), methotrexate (P=0.001) and leflunomide (P=0.012). Multivariate analysis identified limited SSc(OR=3.1), neoplasia(OR=3.4), and use of prednisone(OR=8.2) and leflunomide(OR=5.5) with overlap syndrome. No worse prognosis was observed. CONCLUSION: Overall, Brazilian SSc patients with overlap syndrome have distinct clinical characteristics, but do not have a worse prognosis when compared to those without overlap syndrome.