Background: Early stage (I/II) CRC is traditionally associated with relatively good prognosis at 90% relative survival. The probability of non-cancer death in CRC patients is associated with comorbidity burden; however, there is paucity of data evaluating this association in colon versus rectal cancer. This study examines the impact of comorbdity on 5-year mortality and cause of death after resection for early stage CRC. Methods: Linked patient-level data from the New York State Cancer Registry & Statewide Planning and Research Cooperative System was queried for 2004-2013 patients who underwent colectomy or proctectomy for Stage I-II CRC who survived beyond 30 days. Comorbidity burden was defined as the sum of Elixhauser Comorbidites plus steroid use, MI history, CVD (cardiovascular disease), and dementia to capture maximum number of unique comorbidities and characterized as low (0-1 comorbidity), moderate (2-3 comorbidities), and high (4+ comorbidities). Causes of death were evaluated according to comorbidity group and colon versus rectal cancer. Results: 24,643 (colon 21,384, rectal 3,250) met inclusion criteria, of which 5,464 (22%) died within 5 years. While both colon cancer (CC) and rectal cancer patients (RC) had identical overall mortality (22%), significant differences existed in the proportion of deaths due to the primary cancer with disease-specific mortality of 7% for CC and 11% for RC. Deaths due to CC decreased while CVD causes increased with escalating comorbidity burden. Deaths due to RC accounted for nearly 50% of all deaths even with increasing comorbidity burden (Table). Conclusions: CC is the predominant cause of 5-year mortality in early stage patients with low comorbidity burden while CVD drives mortality in high comorbidity burden patients. In contrast, RC drives early stage mortality regardless of the comorbidity burden; thus, emphasizing the importance of tailored survivorship programs to each cancer.