The aim of this study was to compare the 2-year functional performance and quality of life in patients with operable squamous cell carcinoma of the esophagus, who have received either surgery or definitive chemoradiation (CRT). The functional outcomes and quality of life in patients receiving esophagectomy or definitive CRT is uncertain. Data were extracted from the database of a prospective randomized controlled trial that included patients with resectable mid or lower thoracic esophageal cancers. The patients were randomized to either standard esophagectomy or definitive CRT. Quality of life assessments were performed using the EORTC QLQ-C30 and QLQ-OES24 modules. Other functional assessments included pulmonary and eating functions. From July 2000 to December 2004, a total of 81 patients were enrolled into the study. No significant longitudinal changes were detected in the global health status in both groups upon available follow-up. Surgery was associated with worsened physical functioning and fatigue symptoms up to 6 months after treatment (P < 0.001 and P = 0.021, respectively) and these scales improved at 2 years. In terms of pulmonary function, dyspnoic and coughing symptoms were significantly worsened 3 months after surgery (P = 0.024 and P = 0.036, respectively) whereas symptoms in the CRT group progressively deteriorated over time. Concerning the eating function, both groups had improvements in dysphagia but there were frequent need for endoscopic intervention. This study has been registered with clinicaltrials.gov and the clinicaltrials.gov ID number is NCT01032967. Neither surgery nor definitive CRT significantly impaired the global health status of patients. Surgery was associated with a short-term negative impact in some aspects of health related quality of life assessments but these changes became insignificant 2 years after treatment. However, CRT was associated with progressive deteriorations in pulmonary function in the longer term.