Objective This study investigated the prognostic impact of multimodality therapies in locally advanced thymomas. Methods From January 1990 to January 2010, clinicopathological, surgical, and oncological features were retrospectively reviewed in a cohort of 370 Masaoka-Koga stage III thymomas (World Health Organization classification A to B3) collected from 37 institutions. A multivariate Cox proportional hazard model was created to identify independent predictors of overall, cancer-specific (CSS), and relapse-free survivals. Furthermore, a propensity score-matching analysis for exposure to adjuvant (AT) therapy was generated. Results Induction therapy and AT were administered to 88 (24.9%) and 245 (69.4%) patients, respectively. Overall, 5- and 10-year overall survival, CSS, and relapse-free survivals were 82.8%, 88.4%, and 80.0%, and 68.9%, 83.3%, and 71.5%, respectively. At multivariable analysis performed in the matched cohort, AT was confirmed as the strongest predictive factor for overall survival (hazard ratio, 2.83; 95% confidence interval, 0.88-9.12; P =.08) and CSS (hazard ratio, 4.70; 95% confidence interval, 1.00-22.2; P =.05). Pathologic T classification (according to International Association for the Study of Lung Cancer and International Thymic Malignancy Interest Group TNM staging proposal) was an independent factor for relapse (hazard ratio, 8.69; 95% confidence interval, 1.08-70.04; P =.04). When CSS was adjusted for T classification, AT confirmed a significant survival advantage for pT3 tumors (P =.04). On the other hand, for thymomas larger than 5 cm, stratifying for tumor size and AT did not affect 5-year CSS (P =.17). Conclusions Our results indicate that AT is beneficial for locally advanced thymomas, mainly for specific pathologic features (pT3 or tumor size smaller than 5 cm). Further larger studies are needed to confirm these data. © 2016 The American Association for Thoracic Surgery.