ABSTRACT: Despite the number of publications on orbital decompression surgery for thyroid eye disease, there are few comparative studies and most studies are underpowered. The goal of the study is to use multivariable analysis to identify independent patient and disease-related predictors of response to decompression surgery and of need for secondary decompressions.The authors retrospectively reviewed all patients who underwent transorbital thyroid-related orbital decompression surgery at the Kellogg Eye Center of the University of Michigan between 1999 and 2014. Demographic, medical, and surgical covariates were collected. Decompression techniques included medial, lateral, and balanced decompressions, with or without orbital fat removal. Main outcomes included proptosis reduction and secondary decompressions, both analyzed at the orbital level. Univariate and multivariable analyses (with adjustment for interorbit correlation) were conducted to determine predictors of the outcomes of interest.Mean proptosis reduction was 3.8?±?2.4?mm (mean ± standard deviation, N = 420 orbits). The secondary decompression rate was 13.8% (82/594). On multivariable mixed linear regression, larger preoperative proptosis (p < 0.0001), balanced decompression (p = 0.0002), thyroid eye disease duration < 4 years (p = 0.0093), and history of orbital radiation (p = 0.0111) were all predictive of greater proptosis reduction. On multivariable survival modeling, factors associated with increased hazard for secondary decompression include younger age (p = 0.0434), larger preoperative proptosis (p = 0.0001), unilateral decompression (p = 0.0272), preoperative steroid treatment (p = 0.0200), and normal thyroid function (p = 0.0148). Factors associated with decreased hazard include adjunctive fat decompression (p = 0.0004), balanced decompression (vs. lateral, p = 0.0039), and African-American ethnicity (p = 0.0076).Despite a diverse study cohort, the authors have identified factors associated with clinically relevant outcomes of decompression surgery for thyroid eye disease, including proptosis reduction and incidence of secondary decompression. Randomized controlled trials of different treatment algorithms for TED are needed to devise optimized guidelines for individualizing surgical care.