Epidemiologic studies of colorectal neoplasia have usually examined body mass index as a risk factor, but not other aspects of obesity. During 1991–1993, the authors obtained weight histories and comprehensive covariate data from men and women aged 50–75 years who underwent sigmoidoscopy at a health maintenance organization in southern California. Using 483 cases with adenomas and 483 controls, measures of obesity (body mass index), positive energy balance (net weight gain in the past 10 years), and weight variability (large weight changes) were each independently related to adenoma prevalence. Compared with subjects in the lowest quartile of body mass index, multivariate-adjusted odds ratios for subjects in increasingly higher quartiles were 2.1 (95% confidence interval (CI) 1.4–2.3), 1.8 (1.1–2.9), and 1.7 (1.0–2.8), respectively. Compared with subjects who reported a net weight loss during the 10 years before sigmoidoscopy, subjects with net weight gains of 1.5–4.5 kg or ≥4.5 kg had adjusted odds ratios (95% CI) of 2.5 (1.2–5.6) and 1.8 (0.7–4.4), respectively. Compared with subjects who had no large weight changes during adulthood, subjects with 1–2, 3, or ≥4 changes had adjusted odds ratios (95% CI) of 2.0 (1.0–3.9), 2.5 (1.2–5.5), and 1.5 (0.6–3.6), respectively. Obesity, weight gain, and unstable adult weight may be independently associated with colorectal carcinogenesis. Am J Epidemiol 1998; 147: 670–80.