Background: Disease control and survival outcomes for LAEC are poor despite multimodality treatment with CRT with or without esophagectomy. Without comparative trial data, oncologists select a chemotherapy regimen based on clinical experience and toxicity profile. The present investigation compares LAEC progression free survival (PFS) and overall survival (OS) for CF versus CT. Methods: A retrospective analysis was performed for patients with LAEC from 2003-2012, treated with curative-intent neoadjuvant or definitive concurrent CRT with either CF or CT. Chi-squared tests, Fisher’s exact tests, and t-tests were used to identify significant differences between treatment groups. The Kaplan-Meier method was used to estimate PFS and OS. Results: Of 149 patients with non-metastatic LAEC, 82 met inclusion criteria (n=38 CF, n=44 CT), with 63, 2, and 2 excluded for non-CF/CT CRT, missing data, and <1 month follow-up, respectively. Treatment groups were well balanced, excepting fewer females, lower prior cancer rate, and longer follow-up for the CF group (Table 1). At a median follow-up of 22.7 months (range, 1.8-132.1, median follow-up 58.6 for survivors), 48 patients experienced recurrence (22 CF, 26 CT), and 63 patients died (29 CF, 34 CT). No differences in PFS or OS were demonstrated between treatment groups (Table 1). Conclusions: The present study failed to detect a disease control or survival difference between CF and CT as a component of CRT in neoadjuvant or definitive settings for LAEC. Until randomized trial data are available, oncologists may elect CF or CT based on clinical situations and anticipated sequelae.