Background: The long-term functional outcome after thoracoabdominal resection has to be better evaluated. A study was performed to evaluate patients after a similar operation both in terms of physical function and health-related quality of life (HRQL). Methods: Eighteen patients were evaluated 2 years after a thoracoabdominal resection. Respiratory function, physical performance and range of motion in shoulder, thorax and spine were recorded. HQRL was assessed by EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) and EORTC QLQ-OES18 (Oeophageal module). Results: Two years after surgery, respiratory function (forced vital capacity and forced expiratory volume in 1 s) was significantly impaired compared to preoperative values (p < 0.05). The physical performance was significantly reduced as measured by a functional stand-up test (p < 0.05) and the handgrip force (p < 0.001). Shoulder range of motion, thoracic lateral flexion and C7 to wall were within normal ranges, thoracic flexion significantly greater (p < 0.01) but chest expansion significantly decreased (p < 0.01) compared to controls. HQRL was comparable to age- and sex-matched population norms for most of the functions. A clinical significant difference was, however, found for diarrhoea, dyspnoea, appetite loss and fatigue. Conclusion: Within a 2-year period, each individual regains most of the respiratory and physical performances and HRQL after a thoracoabdominal resection.