In a recently reported, randomized trial, it was found that a regimen of irinotecan once every 3 weeks for patients with advanced colorectal carcinoma was associated with a lower incidence of severe diarrhea compared with weekly treatment, and both regimens had similar efficacy. Resource utilization was captured prospectively for all 291 patients who were included in the trial. Utilities were estimated by transformation of the global quality-of-life (QOL) item on the Eastern Organization for Research and Treatment of Cancer QLQ-C30 instrument. Patients in the every-3-week arm incurred an average incremental cost of $1362, because they received higher average weekly doses and because the every-3-week regimen resulted in less toxicity, allowing delivery of 97% of the planned doses compared with delivery of only 75% of the planned doses in the weekly arm. This lower toxicity also resulted in offsetting savings from decreased hospitalization and less requirement for supportive medications. Non-chemotherapy-related treatment administration costs also were lower, because the every-3-week regimen could be delivered with half the number of infusions. Utility declined less in the every-3-week arm, resulting in a saving of 6.3 quality-adjusted days. The base-case cost:utility ratio was $78,627 per quality-adjusted life year for patients on the every-3-week schedule. However, that ratio was very sensitive to the cost of irinotecan. The schedule of irinotecan once every 3 weeks schedule was more costly but achieved lower toxicity, resulting in modestly improved utility. The cost-per-utility ratio was comparable to other commonly accepted contemporary treatments.