Patients undergoing oesophagectomy are at risk of developing Acute Respiratory Distress Syndrome (ARDS), an immune mediated form of severe respiratory failure. The immunomodulatory properties of Vitamin D are increasingly recognised. We hypothesised that preoperative Vitamin D supplementation would reduce levels of perioperative alveolar oedema in patients undergoing oesophagectomy. Vitamin D deficiency is common in patients with and at risk of ARDS. High dose supplementation with cholecalciferol is a safe and effective method of increasing Vitamin D levels. Supplementation reduces perioperative increases in inflammatory alveolar oedema. Circulating levels of the active form of Vitamin D relate to long term post-operative mortality. Patients who survive at least 2 years post-op have higher preoperative circulating numbers of Natural Killer cells. We did not find any evidence of an effect of Vitamin D on Natural Killer Cells. In conclusion, preoperative Vitamin D status relates to perioperative changes in inflammatory alveolar oedema and high dose Vitamin D supplementation is a safe and effective method of improving preoperative Vitamin D status. Preoperative cholecalciferol administration should be considered in patients with and at risk of vitamin D deficiency.