Objective: This study evaluated how sociodemographic variables and disease characteristics of people with scleroderma relate to levels of social interaction anxiety, and whether these associations are moderated by gender. Methods: Cross-sectional baseline data were analyzed from 1,554 patients. Sociodemographic and disease variables were analyzed as predictors of SIAS scores, with gender considered as a moderator, using hierarchical multiple and logistic regression analyses. Results: For the SIAS, there was no significant difference in total scores between men and women. Across all analyses, age and education were significantly negatively related to SIAS total scores. Both appearance-related and appearance-unrelated symptoms were significantly positively related to SIAS scores, with more symptoms of both types associated with higher levels of social anxiety. Patients with gastrointestinal symptoms, including presence of diarrhea, bloating and/or constipation and/or presence of early satiety and/or vomiting due to SSc, showed significantly higher levels of social interaction anxiety than patients without these symptoms. Conclusion: Overall, patients with SSc had low levels of social interaction anxiety. Presence of symptoms within patients that cause changes to their appearance may impact their social interaction anxiety levels. There were no specific symptoms related to appearance specific to this study that seemed to be more associated with social interaction anxiety than others. However, the number of symptoms present was predictive of social interaction anxiety levels, suggesting that the amount of challenges faced may be of notable importance rather than there being one specific symptom related to social distress. Appearance-unrelated symptoms were also predictive of social interaction anxiety. Gastrointestinal problems seem of notable importance, and patients who experience things such as diarrhea, bloating, constipation, early satiety, or vomiting had higher levels of social interaction anxiety than those with other symptoms that are not related to appearance. These types of gastrointestinal distress may make patients more prone to social problems. The identification of the possible existence of social interaction anxiety within patients with SSc and the understanding of what aspects of the disease may contribute to this anxiety may allow researchers to identify patients at need for intervention and who may be risk for scleroderma-related social difficulties.