Background In patients with thymic neoplasms, the pleural space is a frequent site of either synchronous or metachronous tumor dissemination after surgical resection. The objective of this study was to identify factors that predict pleural dissemination, which would allow for better surgical planning and consideration of novel adjuvant or surveillance strategies. Methods A retrospective review of a prospective database (2000 to 2014) was performed to identify patients with thymic tumors (excluding neuroendocrine). Demographic, clinical, and pathologic data were reviewed. Multivariable Cox regression analysis was performed to determine independent predictors of pleural implants (either occult synchronous or metachronous). Univariate predictors (p < 0.20) were selected for inclusion in a multivariable model. Receiver operating characteristic (ROC) curve was used to assess the effect and cutoff value of tumor size on the incidence of pleural metastasis. Results One hundred sixty-two patients with thymic tumors were identified. Pleural deposits were incidentally identified intraoperatively in 4 patients (2.5%) and developed during follow-up in 15 patients (10%), with a median follow-up of 34 months (interquartile range, 12 to 71). Univariate predictors of pleural metastasis were macroscopic capsular/organ invasion, preoperative core/surgical biopsy, induction therapy, pathologic tumor size, and World Health Organization type B3/C. In the multivariable model, core/surgical biopsy (hazard ratio [HR] 9.45, p = 0.002), macroscopic capsular invasion (HR 10.18, p = 0.008), and larger tumor size (HR 1.34, p = 0.044) were found to be independent predictors of pleural metastasis. The relation between the pathologic tumor size and development of pleural metastasis was further investigated with the ROC curve (area under the curve 0.78, p < 0.001), and the cutoff tumor size that gave the best combined sensitivity and specificity was 6.5 cm. Overall survival of patients with pleural implants was 88% and 50% at 5 and 10 years, respectively. Five- and 10- year disease-free survival for the whole cohort was 80% and 30%, respectively. Conclusions Development of pleural metastasis is predictable. Pathologic tumor size, an independent predictor of pleural implants, can be assessed intraoperatively. Because preoperative core needle biopsy is also an independent predictor of pleural dissemination, its use and execution should be carefully considered. Pleural exploration at the index operation should be considered in high-risk patients. Further studies are needed to confirm these findings and to assess the role of novel therapeutic strategies in reducing pleural disease.