OBJECTIVES: Examine treatment combinations and mortality rate of colorectal cancer (CRC) patients in the U.S. veteran population.  METHODS: Adult patients with at least one primary CRC diagnosis and CRC treatment (5-fluorouracil [5-FU]/LV [leucovorin, levoleucovorin]+/-biologics; Irinotecan [IRI]+/- biologics; Oxaliplatin [OX]+/-biologics; IR+OX [IROX]+/-biologics; or biologics only) were selected (01APR2006-30SEP2012) from the U.S. Veterans Health Administration database. The first observed treatment date was designated as the index date. Patients were followed until the earliest of death, or end of enrollment or study period. Patients were assigned to one of four cohorts based on treatment line (TL) number. Treatment combinations, length of therapy and incidence rate of death were calculated.  RESULTS: A total of 11,078 patients were included for study, with the majority treated with one TL (63%), 22% with two, 8% with three and 7% with four TL. The most frequently prescribed treatment was 5FU/LV in all first TL (1 TL: 65.8%; 2 TL: 62.3%; 3 TL: 50.1%; 4 TL: 41.0%). Patients with three or four TL were prescribed significantly more OX+biologics for the first TL than patients with one or two TL. During the second TL, 5FU/LV and OX were most frequently prescribed. More variances were observed in the third and fourth TL. Length of therapy for each TL ranged from 86 to 104 days. The incidence rate of death was similar between patients with one and two TL (19.66 per 100 patient years), and higher for patients with three (26.28) and four TL (22.41).  CONCLUSIONS: