Peroxisome proliferator–activated receptor-δ (PPAR-δ; also known as PPAR-β) is expressed at high levels in colon tumors, but its contribution to colon cancer is unclear. We examined the role of PPAR-δ in colon carcinogenesis using PPAR-δ-deficient (Ppard^−/− ) mice. In both the Min mutant and chemically induced mouse models, colon polyp formation was significantly greater in mice nullizygous for PPAR-δ. In contrast to previous reports suggesting that activation of PPAR-δ potentiates colon polyp formation, here we show that PPAR-δ attenuates colon carcinogenesis.