Background: Colon cancer ranks third in cancer mortality and estimated new cases in the United States. Along with the improved treatment and increased participation in screening, there are more than 1.5 million survivors. Venous thromboembolism (VTE) is associated with cancers due to various mechanisms that are common with arterial thromboembolism. Still, there are limited population-based studies on the risk of myocardial infarction (MI) and heart failure (HF) in colon cancer. Methods: Retrospectively we analyzed data from a nationwide commercial database (Explorys, IBM) from 1999 to October 2022. It gathers records from 26 healthcare systems in 50 states with nearly 80 million patients. We identified adults over 18 years old with colon cancer, MI, and HF. In addition, we obtained data on risk factors, including sex, age over 65 years, hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), atrial fibrillation, obesity, and tobacco use. Multivariable logistic regression (MLR) was used to adjust for the variables collected. All tests were two-sided, and a p-value ≤ 0.05 was considered statistically significant—data presented as odds ratio (OR) with a 95% confidence interval (CI). Results: A population of 69,339,860 was included. Colon cancer was diagnosed in 304,650 (0.4%), MI in 1,691,900 (2.4%), and HF in 2,415,450 (3.5%). Males made 45%. The colon cancer group, compared to the background population, had a higher prevalence of patients aged over 65 years (66.8% vs. 30.7%), HTN (61% vs. 21.1%), HLD (50.7% vs. 16.9%), DM (31.4% vs. 8.8%), obesity (20.7% vs. 8.0%), and tobacco use (12.5% vs. 6.6%). MLR of variable studies (Table). Colon cancer was significantly associated with MI and HF. Conclusions: This is the largest population-based study of the risk of MI and HF in colon cancer in the United States. After adjustment for established risk factors that may confound the result, colon cancer was independently associated with a significant increase in the risk of MI and HF. Raising awareness among oncologists and cardio-oncologists' involvement at the time of diagnosis is essential to optimally and aggressively manage modifiable risk factors. Prospective studies are needed.