OBJECTIVES: Colorectal cancer (CRC) ranks third in prevalence and cancer deaths among all cancers in the United States. Nearly one fourth of CRC patients are diagnosed at metastatic stage (mCRC), which has a poor prognosis and an overall survival of 5% to 8% at five years. Over the last decade multiple chemotherapies and targeted biologics have been approved for mCRC and patients receive an array of these treatments in various combinations, with limited evidence. The study examines current usage patterns by line of treatment for elderly mCRC patients. METHODS: A retrospective observational cohort study was conducted for mCRC patients diagnosed from January 2004 through December 2009 using the Surveillance Epidemiology and End Results-Medicare linked database. Systemic chemotherapies and targeted biologics currently approved by the Food and Drug Administration for treatment of mCRC patients were included. The first three lines of treatment administered to elderly mCRC patients were empirically identified. RESULTS: The most common first line of treatment for mCRC patients (n=4,603) was bevacizumab + fluorouracil + oxaliplatin (24%), followed by fluorouracil + oxaliplatin (23%). Bevacizumab + fluorouracil + oxaliplatin (18%) and bevacizumab + fluorouracil + irinotecan (15%) were the most administered second line of treatments, while cetuximab + irinotecan and bevacizumab + fluorouracil + irinotecan were the commonly administered third line regimens (15% each). Of 4,603 mCRC patients who received first a line of treatment, 2,708 (59%) continued to receive a second line of treatment, 1,480 (32%) received a third line of treatment, and 1,895 (41%) did not receive any further line of treatment.  CONCLUSIONS: In accordance with current recommendations and previous studies, fluorouracil + oxaliplatin/irinotecan based regimens with bevacizumab were the most common first and second line treatments. Further exploration of the comparative effectiveness of line of treatments sequencing may yield important information for improving the quality of cancer treatment.