Background: We aimed to assess the risk of chemotherapy- and radiotherapy-related cognitive impairment in colorectal cancer patients. Methods: We randomly selected 40% of colorectal cancer patients from Korean National Health Insurance Database (NHID), 2004-2018 (N=148,848). Patients with one or more ICD-10 diagnostic codes for dementia or mild cognitive impairment was defined as cognitive impairment cases. Patients who were aged 18 or younger, diagnosed with cognitive impairment before colorectal cancer (N=8,225) and did not receive primary resection (N=45,320) were excluded. The effects of each chemotherapy agent on cognitive impairment were estimated. We additionally estimated the effect of radiotherapy in rectal cancer patients. Time-dependent competing risk Cox regression was conducted to estimate overall and age-specific hazard ratios (HR) separately for colon and rectal cancer. Results: In colon cancer, capecitabine and irinotecan was associated with higher cognitive im-pairment, while 5-fluorouracil was not. In rectal cancer, no chemotherapy agents increased the risk of cognitive impairment, nor did radiotherapy. Hazardous association of irinotecan was estimated larger in elderly patients compared with younger counterparts. Conclusion: Heterogeneous associations between various chemotherapy agents and cognitive impairment were observed. Elderly patients were more vulnerable to possible adverse cognitive effects. Radiotherapy did not increase the risk of cognitive impairment.