Abstract Background Since the publication of the CROSS-trial, showing improved survival following neoadjuvant chemoradiotherapy + surgery (CRT-S) compared to upfront surgery (U-S) for esophageal cancer, this neoadjuvant regimen has become standard care in the Netherlands. Given the relatively low R0 rate in the U-S arm (69%) and lymph node yield (LNY) in both arms (15 U-S, 18 CRT-S) observed in the CROSS-trial, the present study aimed to compare survival of patients who underwent CRT-S versus U-S in a tertiary referral center that participated in the CROSS-trial, within the era that the trial was performed. Methods This retrospective study included patients, who underwent an esophagectomy between 2004-2010, and met the CROSS-trial inclusion criteria. Primary outcome was 10-year overall survival (OS), and patients with CRT-S and U-S were compared. Secondary outcomes were R0-resection rate, LNY and positive LNY. Subgroup analyses were performed for histology (adenocarcinoma [AC] and squamous cell carcinoma [SCC] and for surgical approach (transthoracic [TTE] and transhiatal [THE] esophagectomy). Results We included 288 patients: 144 after CRT-S, 144 after U-S. 112 (39%) participated in the CROSS-trial. 10-year OS was not significantly better for CRT-S (40%) versus U-S (34%; p=0.183). In SSC, OS following CRT-S was 49% and after U-S 35% (p=0.228), versus 38% and 34% in AC (p=0.396). Following TTE, OS was better compared to THE in both CRT-S and U-S groups: 44% and 39% (p=0.369) versus 32% and 29% (p=0.590). R0-rates were 96% (CRT-S) and 86% (U-S). Median LNY was equal: 23. 55 (38%) and 100 (69%) patients had positive lymph nodes after respectively CRT-S and U-S. Conclusion This study showed that, with a radical TTE, comparable OS results can be achieved, and therefore CRT may not be indicated in all patients. Further analyses are necessary to identify patients who may benefit from the additional local treatment that CRT is (e.g SCC or involved circumferential resection margin). Additionally, surgical techniques have improved since the CROSS-trial, with less surgical trauma in minimally invasive esophagectomy. This may result in better outcomes for surgery nowadays, indicating the need for further studies in the current era.