Background Low‐dose aspirin and metformin have been individually associated with a reduced risk of cancer. Whether their concurrent use in adults with type 2 diabetes mellitus (T2DM) is associated with a reduced risk of colorectal cancer (CRC) is unclear. Objective Among individuals with T2DM taking metformin, we sought to evaluate the association between low‐dose aspirin versus no aspirin and the risk of CRC. Methods A multiple‐database new‐user cohort study of patients with T2DM taking metformin was conducted between 2007 and 2010 (Clinical Data Analysis and Reporting System CDARS, Hong Kong) and 2007–2016 (The Health Improvement Network THIN, UK). The primary outcome was incident CRC. Patients were followed from index date of prescription until the earliest occurrence of an outcome of interest, an incident diagnosis of any cancer, death, or until 31 December 2019. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Estimates were pooled using an inverse variance random effects model, and heterogeneity was assessed using I2. Results After one‐to‐one propensity‐score matching, 57,534 patients were included (CDARS = 16,276; THIN = 41,258). The median (IQR) follow‐up was 9.3 (6.5–10.7) years in CDARS and 3.2 (1.1–5.8) years in THIN. The concurrent use of low‐dose aspirin and metformin was not associated with a lower risk of CRC compared to metformin only (HR = 0.89, 95% CI 0.75–1.05, I2 = 0%). Conclusion Low‐dose aspirin was not associated with a lower risk of CRC in patients with T2DM taking metformin. Our study does not support the routine use of low‐dose aspirin in this population.