Background: For resectable esophageal or GEJ cancer, trimodality therapy improves survival compared to surgery alone and represents the current standard of care. The optimal CRT regimen for neoadjuvant or definitive treatment of locoregional esophageal or GEJ cancer remains uncertain. Methods: A retrospective comparison of CF and CP for locoregional esophageal or GEJ cancer (2011-2015) was performed. Overall survival (OS) and disease-free survival (DFS) were assessed using multivariable Cox proportional hazards regression, controlling for age, performance status and Charlson comorbidity index. Results: 101 patients (pts) were identified (61 CF, 40 CP). 75% were male. Median age was 62 years (range 30-84). Primary sites were esophageal (52%, with 65% squamous histology) and GEJ (48%). Surgery was undertaken in 34 (56%) CF and 27 (68%) CP pts. Median follow-up was 43 months. Overall, there was a non-significant trend for improved OS with CF compared to CP (HR 0.61, 95% CI 0.33-1.14, p = 0.12). In the subgroup having surgery (N = 61), we found no significant difference in OS (HR 0.99, 95% CI 0.39-2.55, p = 0.99). In the subgroup without surgery (N = 40), CF was significantly superior to CP (HR 0.21, 95% CI 0.08-0.53, p < 0.001). Comparing only pts in this subgroup who received equitable radiation doses (N = 33), CF was still significantly superior to CP (HR 0.09, 95% CI 0.03-0.32, p < 0.001). OS was similar by histology (adenocarcinoma/squamous) in all-comers (p = 0.54), and in CF (p = 0.90) and CP subgroups (p = 0.63). DFS results corresponded with OS. There was a non-significant numerical difference in pCR rates between CF (31%) and CP (18%) (p = 0.35), which were lower than previously reported. Conclusions: Survival is similar for CF and CP CRT regimens in pts undergoing trimodality therapy, but for those who do not proceed to surgery, it appears that CF is more effective than CP. Clinicians may prefer CP for surgical candidates given its favourable toxicity profile. However, when treating with definitive CRT, CF may be preferable to CP as a standard regimen.