Background: Metastatic colon cancer (mCC) patients often receive multiple lines of chemotherapy as treatment (TX) to improve survival or quality of life, yet the “real world” benefits and risks of multiple TX lines have not been fully examined. Methods: Elderly (65+) SEER-Medicare patients diagnosed with mCC in 2003-2007 were followed until death or 12/31/09 to examine the survival benefits for different chemotherapy lines. The median time between diagnosis date and the starting date of 2^nd line was 352 days. Therefore, we restricted comparative analysis of 2^nd and subsequent chemotherapy TX lines to patients who survived at least 1 year after mCC diagnosis date. We used Cox regression framework and adjusted for patients’ TX and censoring histories by using inverse probability weighting method. Separate analyses were conducted for short (2 years) and long-term (5 years) survival to examine different benefits of 2^nd and subsequent chemotherapy lines. Results: Of 2,600 elderly Medicare mCC patients diagnosed between 2003-2007 and who survived at least 1 year, 2,530 were dead by the end of 2009. Significant factors associated with long-term survival were 1^st line therapy(HR = 0.76; p < 0.01), 2^nd line therapy (HR = 0.83; p < 0.01) , and subsequent chemotherapy line therapy(HR = 0.85; p = 0.04), as compared to no therapy, age groups 95⁺ (HR = 3.07; p < 0.01), 85-94 (HR = 1.33; p < 0.01), and 75-84 (HR = 1.10; p = 0.04) as compared to 65⁺-74, Asian vs. White (HR = 0.71; p < 0.01), and zip code level household median income (HR = 0.98; p = 0.01). For short-term survival, the benefits of 2^nd and subsequent chemotherapy lines were maintained until month 29. Patients with poor performance status were less likely to proceed to 2nd line therapy. No statistically significant variables predicting receipt of subsequent chemotherapy lines were identified. Conclusions: Among elderly Medicare mCC patients who survived at least 1 year after diagnosis, 1^st line therapy improved both short and long-term survival. 2^nd and subsequent chemotherapy line therapy reduced short-term mortality (2 years); however, they didn’t add any additional long term survival benefit (5 years) as compared to 1^st line therapy.