Background and Aims: The increasing prevalence of adolescent obesity affects adult health. We investigated the association of adolescent overweight with colorectal cancer incidence in a large cohort of males. Methods: Body mass index (BMI) was measured in 1.1 million Jewish Israeli males who underwent a general health examination at ages 16 to 19 between 1967 and 2005. Overweight was defined as BMI ≥85th percentile of the standard U.S. distribution in adolescence. Colorectal cancer was identified by linkage with the Israel National Cancer Registry up to 2006. The mean follow-up period was 17.6 ± 10.9 years, reflecting 19.5 million person-years. Cox proportional hazards modeling was used. Results: The prevalence of adolescent overweight increased from 9.9% to 16.8% in the first 10 and last 10 annual examination cohorts. Colon (n = 445) and rectal cancer (n = 193) cases were detected. Overweight predicted an increased risk of colon cancer [HR = 1.53; 95% confidence interval (CI), 1.17-2.02, P = 0.002] but not of rectal cancer (HR = 1.09; 95% CI, 0.38-1.73, P = 0.72). The risk was greatest for nonmucinous adenocarcinoma of the colon (HR = 1.68, 95% CI, 1.26-2.23, P = 0.001). The association of BMI ≥ 85th percentile with colon cancer was even more pronounced in analyses that were restricted to men followed until at least 40 years of age [N = 367,478; HR = 1.75 (95% CI, 1.33-2.3, P < 0.001)]. Conclusions: Adolescent overweight is substantially associated with colon cancer incidence in young to middle-aged adults. Impact: These long-term sequelae add to the urgency to seriously address increasing childhood and adolescent obesity with its attendant increasing population impact.