Little is known about the etiology of small intestine cancer. We investigated the association between BMI, mean arterial pressure, and plasma total cholesterol, triglycerides and glucose and risk of small intestine cancer in 807,485 men and women in Me-Can. During follow-up, 339 individuals were diagnosed with small intestine cancer. Positive associations were found for triglycerides and a metabolic score with small intestine cancer risk in women, and glucose was further positively associated with adenocarcinoma of the small intestine in women. Pairwise positive interactions were observed between triglycerides and cholesterol, and between mean arterial pressure and glucose, in relation to small intestine cancer risk in women. No associations were observed in men. We conclude that a healthy lifestyle preventing metabolic aberrations may prevent small intestine cancer in women. The study has been published in the International Journal of Cancer.