This study aimed to describe the correlation between some clinical features and orbital soft tissue volume in Graves orbitopathy (GO). The authors collected computed tomography scans from 56 untreated GO patients and measured fat volume (FV), intraorbital and extraorbital FV (IFV, EFV), bony cavity volume (BV), and extraocular muscle volume (MV) of the 112 orbits by using Mimics software. The ratio of soft tissue volume and BV were used to eliminate the individual variations. Outcomes were compared among groups and were correlated with clinical data, including age, sex, clinical activity score, duration, serum TSH receptor antibody (TRAb) level, body mass index and smoking status. Multivariate linear regression showed that higher MV/BV is associated with higher CAS and TRAb level ( P< 0.001, 0.005, res p ectively). No relationship was found between MV/BV and duration, sex, age, and body mass index. IFV/BV was related to duration (β=0.138, 95% confidence interval: 0.076-0.201, P <0.001), and did not correlate to clinical activity. IFV and MV are positively associated with exophthalmometry ( P =0.009, <0.001, respectively), while orbital bony volume (BV) is negatively correlated with exophthalmometry ( P =0.025). Results suggested TRAb level can impact the severity of GO mainly by affecting extraocular muscle rather than fat tissue. MV of GO is associated with disease activity, whereas IFV is correlated with duration and increases over time.Copyright © 2022 by Mutaz B. Habal, MD.