We evaluated economic implications of treatment with irinotecan, following a RCT which demonstrated significantly increased survival at 1 year with irinotecan (45%) compared to infusional 5-fluorouracil (5-FU) (32%) in patients with metastatic colorectal cancer. Medical care consumption data were collected prospectively alongside the trial, with 256 patients followed for a median of 10 months. Follow-up was prolonged beyond treatment failure and medical care consumption was not protocol driven, enabling a realistic evaluation of economic implications. Medical care consumption associated with chemotherapy administration was lower with irinotecan as compared with infusional 5-FU. The cumulative number of days in hospital due to treatment toxicity and cancer complications, which is the key cost driver, was 14.4 (95% CI: 10.7-18.1) with irinotecan versus 17.5 (95% CI: 11.7-23.3) with infusional 5-FU. Thus, the survival benefit with second-line irinotecan compared to infusional 5-FU in patients with advanced colorectal cancer was achieved without increasing medical care consumption.