BACKGROUND: Calcium can reduce the risk of colorectal tumors by binding secondary bile and fatty acids, which leads to antiproliferative effects in the bowel, or by acting directly on the colonic epithelium, which affects differentiation and apoptosis. OBJECTIVE: We investigated calcium intake and risk of colon adenoma to evaluate the association of calcium intake with early stages of colorectal tumor development. DESIGN: We compared the supplemental and dietary calcium intakes of 3696 participants with histologically verified adenoma of the distal colon (ie, descending colon, sigmoid colon, or rectum) with the calcium intakes of 34 817 sigmoidoscopy-negative control participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Calcium intake was assessed at study entry with a 137-item food-frequency questionnaire and additional questions on the amount and duration of calcium supplement use. RESULTS: After adjustment for known risk factors, adenoma risk was lower by 12% for participants in the highest quintile of total calcium intake (>1767 mg/d) than for participants in the lowest quintile (<731 mg/d) (odds ratio: 0.88; 95% CI: 0.76, 1.02; P for trend = 0.04). The protective association between total calcium and colorectal adenoma was largely due to calcium supplement use, with a 27% decrease in adenoma risk for participants taking >1200 mg/d than for nonusers of supplements (odds ratio: 0.73; 95% CI: 0.56, 0.91; P for trend = 0.005). The protective associations of total and supplemental calcium were strongest for colon adenoma (descending and sigmoid colon). CONCLUSION: High calcium intake, particularly from supplements, is associated with a reduced risk of distal colorectal adenoma.