Background: Thymic carcinoma is a rare neoplasm. Minimal information exists regarding second-line chemotherapy efficacy in patients with previously treated advanced thymic carcinoma. Methods: We performed a multi-institutional, retrospective study named NEJ023 for patients with advanced thymic carcinoma, excluding thymoma type A/B. The patients with no indication for curative treatment were treated with chemotherapy from 1995 to 2014 at 40 institutions of the North East Japan Study Group (NEJSG). Data were obtained from medical records and included demographic, clinicopathologic, treatment, and outcome information. The Kaplan–Meier method was used to calculate overall survival (OS) and progression-free survival (PFS). Results: Among 324 patients recruited for this study, 192 patients were received second-line chemotherapy. Patient characteristics were: median age 61 years (range 14–84); male/female 72%/28%; PS 0–1/2–3/unknown 77%/15%/8%; Masaoka stage IVa/IVb/postoperative recurrence/other 28%/49%/19%/4%; UICC TNM stage IV/postoperative recurrence/other 78%/19%/3%. Among 192 patients, 70% had squamous cell histology and 10% had poorly-differentiated neuroendocrine carcinoma. Regimens for second-line chemotherapies were platinum doublets in 58% of patients, monotherapy in 29%, and other multi-agent chemotherapy (e.g., cisplatin, doxorubicin, vincristine, and cyclophosphamide: ADOC) in 13%. The median follow-up time was 18.6 months (m), and median OS from the start of chemotherapy was 22.4 m (95% confidence interval, 17.5–26.7). There were no significant differences in the response rate (RR) and OS between monotherapy and multi-agent chemotherapy (platinum doublets and other multi-agent chemotherapy) (RR: 18.2% vs. 17.5%, p = 0.871, median OS: 21.4 m vs. 22.5 m, hazard ratio = 1.164, p = 0.440). Notably, S-1-administered 18 patients, RR and median PFS and OS were 38.9% and 8.3 m and 21.4 m, respectively. Conclusions: These results suggested that adequate efficacy can be achieved by monotherapy for previously treated patients with advanced thymic carcinoma. S-1 might be a promising agent for these patients. Clinical trial information: UMIN000015649.