OBJECTIVES: Compare demographic and clinical characteristics among colorectal cancer (CRC) patients with different treatment lines (TL) in the U.S. veteran population. METHODS: Adult patients with at least one administration of CRC treatment were selected from the U.S. Veterans Health Administration database (01APR2006-30SEP2012). The first observed treatment date was designated as the index date. Patients were required to have continuous pharmacy and medical benefits at least 6 months pre-index date (baseline) and were followed until the earliest of death, or end of enrollment or study period. At least one primary CRC diagnosis code was required during the baseline period. Four cohorts were created based on the number of TL. Demographic and clinical characteristics were compared among patients with one, two, three, or four TL using appropriate statistical tests.  RESULTS: A total of 11,078 patients were included in the study sample (63% with one TL; 22% with two TL; 8% with three TL; 7% with four TL). Patients treated with three or four TL were similar in age (3 TL: 63.8 years; 4 TL: 63.3) but significantly younger compared to patients with one or two lines (1 TL: 67.0; 2 TL: 64.6). Patients with 3 or 4 TL had a lower Chronic Disease Score, and lower rates of hypertension and stroke. During the 6-month baseline period, patients with 1 TL had much longer hospitalization stays and a higher rate of inpatient visits (7.3 days, 57.4%) compared to patients in other cohorts. A similar trend was found in baseline healthcare costs, where patients with 1 TL incurred the highest costs ($38,010) compared to the other three cohorts (2 TL: $34,332; 3 TL: $33,738; 4 TL: $31,120; all p-values<0.002).  CONCLUSIONS: CRC patients with more than two TL were younger and had less comorbid conditions than patients with one or two TL.