Recently, the potential health effects of trans-fatty acid consumption have raised concerns. A few studies have examined the risk of colorectal cancer with increasing consumption of trans-fatty acids, but none investigated the risk of rectal cancer, which may have different risk factors than colon cancer. Our objective was to explore the relationship between trans-fatty acid consumption and distal colorectal (sigmoid, rectosigmoid, and rectal) cancer using a case-control study of Whites (n = 1,516) and African Americans (n = 392) in North Carolina from 2001 to 2006. Matched cases and controls were interviewed about demographic information, lifestyle factors, and diet. White cases reported higher mean consumption of trans-fatty acid than White controls, but mean consumption was similar for African American cases and controls. Relative to the lowest quartile, the highest quartiles of energy-adjusted trans-fatty acid consumption were positively associated with distal colorectal cancer for Whites [adjusted ORs for the third and fourth quartiles are 1.54 (95%CI: 1.12, 2.13) and 1.45 (95%CI: 1.04, 2.03), respectively]. Consumption was not associated with distal colorectal cancer in African Americans [adjusted ORs for the third and fourth quartiles are 0.98 (95%CI: 0.47, 2.05) and 0.87 (95%CI 0.42, 1.81), respectively]. In conclusion, high consumption of trans-fatty acids was positively associated with distal colorectal cancer among Whites.