OBJECTIVE: To examine and compare treatment outcomes and economic benefits in metastatic colorectal cancer with an oral fluoropyrimidine, capecitabine, versus comparison therapies. METHODS: A retrospective, matched-cohort study design was used to abstract medical and retail pharmacy claims records of 271 metastatic colorectal cancer patients from a managed care, disease management database over a 30-month period. Patients were matched in two study cohorts based on their treatment, capecitabine (n=78) vs. 5FULV +/- irinotecan (CPT) (n=193). The 5FU comparison cohort was comprised of three therapy sub-groups: 5FULV (n=78), 5FULV then CPT (n=78), and 5FULV plus CPT (n=37). Time to treatment discontinuation and survival were compared between cohorts. The total direct cost of cancer care was captured through reimbursement claims. Cost-effectiveness (cost per treatment duration) was calculated for both cohorts. RESULTS: Patients were well matched by age, gender, metastases and co-morbidity status. Time to treatment discontinuation with capecitabine was not significantly different than the comparison cohort (79 days vs. 104 days). Median estimated survival for capecitabine was favorable relative to the comparison cohort (599 days vs. 530 days, p=0.05). The total direct cost of cancer care per patient was lower for capecitabine ($6,007 vs. $13,339). Consequently cost-effectiveness ratio per patient was lower for capecitabine than for the comparison cohort ($76 vs. $128) and remained favorable for capecitabine versus individual therapy subgroups (5FULV: $75, 5FULV then CPT: $162, and 5FULV plus CPT: $228). The total cost for chemotherapy and supportive care with capecitabine was much lower per patient ($3,264 vs. $10,112). Savings with capecitabine were primarily realized from reduced cost of chemotherapy ($2,416 vs. $8,499), anti-emetics ($83 vs. $999) and anti-infective agents ($19 vs. $69) relative to comparison therapies. CONCLUSION: Oral administration of capecitabine offers similar clinical outcomes and superior cost-effectiveness relative to comparison therapies.