OBJECTIVE: Epidemiologic studies on calcium, vitamin D and colon cancer are inconsistent, whereas experimental studies more regularly show a protective effect. To evaluate potential sources of inconsistencies, data from a large case-control study were analyzed, stratifying on potential effect modifiers. METHODS: Data were collected by certified interviewers in Northern California, Utah and Minnesota. Analyses included 1993 incident colon cancer cases and 2410 population-based controls. Multivariate logistic regression models included age, sex, BMI, family history, physical activity, intake of energy, dietary fiber, aspirin and NSAIDs. RESULTS: Dietary calcium was inversely associated with colon cancer risk in men (OR highest vs lowest quintile = 0.6, 95␌I = 0.5-0.9) and women (OR = 0.6, 95␌I = 0.4-0.9). No statistically significant associations were observed for dietary vitamin D or sunshine exposure. Consumption of total low-fat dairy products was associated with a statistically significantly decreased risk in men and women (ORs highest vs lowest category of intake = 0.8 and 0.7 respectively). Calcium supplement use was inversely associated with risk in both sexes (ORs use vs non-use = 0.8). Vitamin D supplements were inversely associated with risk in men (OR = 0.5) and women (OR = 0.6) but confidence limits included 1.0. CONCLUSIONS: These data provide additional support of an inverse association between high levels of calcium intake and colon cancer risk.