Background: Smoking adversely affects the course and severity of Graves' orbitopathy (GO). Cigarette smoke enhances adipogenesis in cultured human orbital fibroblasts. The present study tested our hypothesis that smoking is associated with increased orbital fat in GO patients. Methods: This was an observational case series study. In 95 consecutive patients with untreated GO, the ratios of fat volume/orbital volume (FV/OV) and muscle volume/OV (MV/OV) were calculated with validated software. The most affected orbit of each patient was chosen for analysis. Patients were divided into two groups based on smoking behavior. One group was current smokers (Sm+) and the other were those who never smoked or those who had not smoked for at least 1 year (Sm-). Patients were grouped in tertiles of FV/OV and MV/OV and contrast in OVs between the Sm+ and Sm- group. The main characteristics of GO were analyzed using Jonckheere-Terpstra trend analysis and Mann-Whitney U-test. Results: The proportion of current smokers was not different in GO patients when divided in tertiles according to their FV/OV. In contrast, analysis of MV/OV tertiles showed a trend to a higher prevalence of current smokers in patients with larger MVs. Smoking did not influence FV, but the Sm+ group had significantly larger MVs than the Sm- group. Conclusion: Smoking is associated with an increase in extraocular MV in untreated patients with GO and not with an increase in FV.