Despite advancements in treatment strategies, the mortality from colorectal cancer (CRC) remains high. Evidence suggests that aspirin (ASA) may have a protective effect on CRC incidence and metastasis through various mechanisms. The 2016 to 2020 National Inpatient Sample was used to identify adult patients (age above 18 y) with the principal diagnosis of CRC. Patients were stratified into 2 groups based on ASA use. The outcomes studied were in-hospital mortality and rates of total, gastrointestinal (GI), non-GI, and lymphoid metastasis. A multivariate logistic regression analysis was performed to evaluate the impact of ASA use on outcomes after adjusting for patient demographics, comorbidities, and the Elixhauser Comorbidity Index (ECI). Of the 814,270 patients, 88,620 (10.8%) used ASA, with the majority being aged above 65 years (78%), male (57%), white (77.6%), and had Medicare insurance (74.5%). There was a higher prevalence of Diabetes mellitus, Hypertension, Chronic pulmonary disease, Coronary artery disease, Chronic kidney disease, Chronic heart failure, Obesity, and Smoking among aspirin users than among non-ASA users. Patients who used ASA had a lower prevalence of total (47.3% vs. 32.5%, P<0.001), GI (22.2% vs. 32.4%, P<0.001), non-GI (9.9% vs. 15.3%, P<0.001), and lymphoid (9.3% vs. 10.9%, P<0.001) metastasis compared with those who did not use ASA. After adjusting for confounding factors, patients with ASA use had lower odds of total (aOR: 0.75, 95% CI: 0.72-0.78, P<0.001), GI (aOR: 0.74, 95% CI: 0.71-0.77, P<0.001), non-GI (aOR: 0.72, 95% CI: 0.68-0.77, P<0.1), and statistically insignificant odds of lymphoid (aOR: 0.95, 95% CI: 0.90-1.00, P=0.098) metastasis. The use of ASA is associated with a decrease in the prevalence of metastasis among individuals diagnosed with CRC, but additional studies are required to elucidate the mechanism and duration of therapy needed to be effective.