Background Endoscopic mucosal resection (EMR) is the standard treatment for complex colorectal lesions, offering an effective minimally invasive alternative to surgery. However, the incidence of colorectal cancer (CRC) arising after EMR is incompletely characterized across diverse real-world populations.Methods We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Adult patients (≥ 18 years) who underwent colonoscopy or sigmoidoscopy with EMR between January 2016 and January 2017 were included. Patients with a prior diagnosis of inflammatory bowel disease (IBD) or familial adenomatous polyposis (FAP) were excluded. The primary outcome was incident CRC, observed annually from 2018 through 2021. Incidence rates were calculated as cases per 1,000 person-years (PYO), stratified by age group, sex, race, and ethnicity. Temporal trends were assessed using annual percentage change (APC) analysis.Results A total of 4,187 patients were included. The overall post-EMR CRC incidence was 11.85 per 1,000 person-years. Incidence was higher in men (13.61) than women (10.28). Marked racial and ethnic disparities were observed: Hispanic/Latino patients had the highest incidence (28.30), compared to non-Hispanic/non-Latino individuals (12.10). By race, Asian patients had the highest incidence (23.38), followed by Black (11.81) and White patients (10.78). Age-stratified analysis identified the highest incidence in the 40–49-year group (42.2 per 1,000 PYO), with lower rates in the 50–59 (7.8) and 60–69 (9.4) groups, increasing again to 16.8 in the 70–79-year group. Temporal analysis revealed a 27.6% decline in incidence from 30.1 in 2018 to 21.8 per 1,000 PYO in 2021.Conclusion Post-EMR CRC incidence varied substantially across racial, ethnic, sex, and age groups, with notable disparities disproportionately affecting Hispanic/Latino and Asian populations, as well as younger adults. These findings underscore the need for risk-stratified, equity-focused surveillance protocols following EMR and call for prospective research integrating procedural, demographic, and molecular data.