Adiposity has been recognized as a risk factor for colorectal adenoma, but the influence of weight gain, adipose tissue distribution, and possible differences between ethnic/racial and gender groups remains unanswered. The aim of this prospective study was to examine the association between adiposity and weight change and colorectal adenoma risk. Over approximately 10-year period, anthropometric measures and other risk factors were measured at three time points in the multicenter multiethnic Insulin Resistance Atherosclerosis Study cohort. Colonoscopies were then conducted on 600 cohort participants regardless of symptoms whose mean age at colonoscopy was 64 years. Multivariate logistic regression analyses were used to assess the association between colorectal adenomas and measures of adiposity and weight change over the approximately 10-year period before colonoscopy. Obesity was positively associated with risk of colorectal adenomas at the time of colonoscopy [adjusted odds ratio (OR(adj)), 2.16; 95% confidence interval (95% CI), 1.13-4.14] and was stronger in women (OR(adj), 4.42; 95% CI, 1.53-12.78) than in men (OR(adj), 1.26; 95% CI, 0.52-3.07). The risk of adenomas increased among participants who gained weight compared with those who maintained weight over the approximately 5 years (OR(adj), 2.30; 95% CI, 1.25-4.22) and approximately 10 years (OR(adj), 2.12; 95% CI, 1.25-3.62). These associations were similar for both advanced and nonadvanced adenomas. These results suggest a positive association between obesity, weight gain, and colorectal adenoma risk. Stronger associations were observed when obesity was measured at the time of colonoscopy, suggesting that obesity may be a promoting factor in the growth of colorectal adenomas.