Importance: Although aspirin is recommended for the prevention of colorectal cancer (CRC) among adults aged 50 to 59 years, recent data from a randomized clinical trial suggest a lack of benefit and even possible harm among older adults. Objective: To examine the association between aspirin use and the risk of incident CRC among older adults. Design, Setting, and Participants: A pooled analysis was conducted of 2 large US cohort studies, the Nurses' Health Study (June 1, 1980-June 30, 2014) and Health Professionals Follow-up Study (January 1, 1986-January 31, 2014). A total of 94540 participants aged 70 years or older were included and followed up to June 30, 2014, for women or January 31, 2014, for men. Participants with a diagnosis of any cancer, except nonmelanoma skin cancer, or inflammatory bowel disease were excluded. Statistical analyses were conducted from December 2019 to October 2020. Main Outcomes and Measures: Cox proportional hazards models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% CIs for incident CRC. Results: Among the 94 540 participants (mean [SD] age, 76.4 [4.9] years for women, 77.7 [5.6] years for men; 67223 women [71.1%]; 65 259 White women [97.1%], 24 915 White men [96.0%]) aged 70 years or older, 1431 incident cases of CRC were documented over 996463 person-years of follow-up. After adjustment for other risk factors, regular use of aspirin was associated with a significantly lower risk of CRC at or after age 70 years compared with nonregular use (HR, 0.80; 95% CI, 0.72-0.90). However, the inverse association was evident only among aspirin users who initiated aspirin use before age 70 years (HR, 0.80; 95% CI, 0.67-0.95). In contrast, initiating aspirin use at or after 70 years was not significantly associated with a lower risk of CRC (HR, 0.92; 95% CI, 0.76-1.11). Conclusions and Relevance: Initiating aspirin at an older age was not associated with a lower risk of CRC in this pooled analysis of 2 cohort studies. In contrast, those who used aspirin before age 70 years and continued into their 70s or later had a reduced risk of CRC.