Background: Survival differences between left sided (LCC) and right sided colon cancer (RCC) have been previously reported with mixed results. Many used short study periods and did not account for "other cause of mortality" (OCM). The differences in survival may exist irrespective of modern therapeutic agents, with implications for future clinical trial designs. Methods: We sought to assess the trends in the cause- specific and overall survival of colon cancer based on sidedness, using competing risk analysis. A SEER database from 1975 to 2019 was used.Time interval chosen based on clinical adoption of modern chemotherapy (1975-1989 = period A, 1990-2004 = B, 2005-2019 = C). Cox model was used for overall survival (OS), and Fine-Gray competing risk analysis for cause-specific survival (CSS). Adenocarcinoma were included, and primary rectal cancers excluded. Results: Of the 227,637 colon cancer patients, 50.1% were female and 46.2% RCC. Racial distribution of LCC vs RCC; Black-48.5% vs 51.5%, White-53.1% vs 46.9%, API/AN-63.7% vs 36.3%; p < 0.001. Age ≥ 65 were more likely to have RCC vs LCC (51.4% vs 48.6%), LCC common for age 18-49 (64.6% vs 35.4%), 50-64 (62.3% vs 37.7%), p < 0.00l. Females more likely to have RCC (50.4%vs 41.9%; p < 0.001), and males to have LCC (58.1% vs 49.6%;p < 0.001). Median CSS for LCC and RCC was 19.3 and 16.7 years respectively for 1975-1989 but median CSS for period B and C did not reach during study period. Median OS increased over time for both LCC (A = 5.5 yrs.; B = 7.6yrs and C = 10.5 yrs.) and RCC (4.3, 5.8 and 7.5yrs respectively). CSS was better for LCC than RCC for period C (aHR 0.89; 0.86-0.92; p < 0.001). LCC consistently showed superior OS for all study periods. Stage stratification showed worse CSS for localized and regional LCC in the earlier study periods, but the risk attenuated over time. However, left sided distant disease had superior CSS for all periods. Overall survival was better for LCC irrespective of stage, with gradual improvement over time(table 1). Conclusions: Over the past four decades, LCC has shown superior survival over right sided tumors. Furthermore, prognosis between LCC and RCC became more divergent in favor of LCC with the adoption of modern chemotherapy. Clinical trials for colon cancer should consider sidedness when recruiting patients for intervention.