OBJECTIVES: Tegafur with uracil (Uftoral) is one of two oral fluoropyrimidine therapies approved by NICE for the first-line treatment of metastatic colorectal cancer. The other therapy is a 5-fluorouracil pro-drug, capecitabine. The purpose of this study was to compare the cost-effectiveness of tegafur with uracil (when prescribed with folinic acid) against capecitabine and other standard intravenous 5-fluorouracil regimens. METHODS: A literature review was conducted to assess the relative clinical effectiveness of the different therapies under assessment. A similar assessment was completed by Ward et al. Costs were calculated from the UK NHS perspective for the full cost of treatment included drug acquisition, drug administration, and the treatment of adverse events. A cost minimisation analysis was utilised. Direct randomised controlled trial comparisons of the oral therapies with infusional 5-fluorouracil schedules were not available, though this assumes that all treatments are of equal efficacy. RESULTS: The cost-minimisation analysis showed that treatment costs for a 12-week course of capecitabine (£2132) and tegafur with uracil (£1788) were lower than costs for the intravenous Mayo regimen (£3593) and infusional regimens on the de Gramont (£6255) and Modified de Gramont (£3485) schedules over the same treatment period. For tegafur with uracil, this represents a cost saving of £343 versus capecitabine and £1696 versus the modified de Gramont. CONCLUSION: The two oral therapies approved by NICE both result in lower costs to the NHS than intravenous therapies. Tegafur with uracil represents cost savings both per patient, but significant cost savings can be accrued when extrapolated over the whole potential patient population. Differences in this study are primarily driven by drug acquisition cost. This study does not take into account hand and foot syndrome which is a prominent side effect in all treatments except tegafur with uracil and results in resource utilisation and nurse time.