Objective: To undertake a cost-consequence analysis of direct medical costs in the treatment of advanced oesophagogastric cancer based on the REAL 2 randomized clinical trial, which demonstrated non-inferiority when oral capecitabine was substituted for infusional 5FU as part of the standard regimen, ECF. Methods: Direct medical costs (2007 CDN$) from the perspective of the Canadian public health system were applied to resources (e.g., study treatment, toxicity management) obtained from REAL 2 trial data available in the public domain. Complete drug delivery was assumed. Mean overall costs per patient were estimated over six cycles, corresponding to treatment duration. Results: The mean total cost per patient treated with ECF was $9065 and $9268 for ECX. The major driver of cost in the ECX arm is chemotherapy drug, $5472 for capecitabine versus $2400 for infusional 5FU (6 cycles). This is offset by the cost of chemotherapy administration, $1551 for ECF compared to $671 for ECX, and central venous access costs, $1230 for ECF. Additional line complication and hospitalization data were not available and therefore not included in these estimates. Limited data on toxicity management, (e.g. febrile neutropenia, anemia, thromboembolism), are available, and cost estimates are $2,955 for ECF and $2433 for ECX-treated patients. Conclusion: ECX has similar efficacy to ECF in the REAL 2 trial, but has potential advantages in terms of patient preference and convenience of an oral therapy. In addition, oral therapy decreases hospital resource consumption. While drug costs for ECX are greater, costs for chemotherapy administration and line-related costs are substantially less, and underestimated in this analysis. Substituting capecitabine for infusional 5FU in the ECF regimen is an attractive and affordable alternative for patients with advanced oesophagogastic cancer.