To compare the proportion of interval left-sided colorectal cancers (CRCs) after flexible sigmoidoscopy vs colonoscopy in older patients and to identify factors associated with interval CRC.Using the Surveillance, Epidemiology, and End Results–Medicare–linked database, we studied patients 67 years or older with left-sided CRC who had at least one lower endoscopy performed within the previous 36 months between July 1, 2001, and December 31, 2005. The CRCs diagnosed within 6 months of lower endoscopy were defined as detected CRCs; CRCs diagnosed 6 to 36 months after lower endoscopy were defined as interval CRCs. The proportion of interval CRCs was calculated as number of interval CRCs divided by number of detected and interval CRCs. The χ 2 test and a multivariate logistic regression model were used in the statistical analysis.Of 15,484 older patients with left-sided CRC, the proportion of interval CRCs after flexible sigmoidoscopy was 8.8% compared with 2.5% after colonoscopy (P<.001). This difference was similar across left colon locations and largest in the descending colon (17.1% vs 3.5%; P<.001). In multivariate logistic regression, the odds of interval CRC after flexible sigmoidoscopy was 3 times as high as that after colonoscopy (odds ratio, 3.52; 95% CI, 2.66-4.65).In older patients with left-sided CRC, the odds of interval CRC after flexible sigmoidoscopy was 3 times as high as that after colonoscopy. Whether this finding reflects differences in bowel preparation quality, sedation use, or depth of insertion warrants future research.