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Purpose: The purpose of this study was to examine whether a hyaluronan-based membrane (Seprafilm Adhesion Barrier) could affect growth and metastasis of colon cancer in a human xenograft/nude mouse model., Methods: Male athymic (nude) mice underwent a midline abdominal incision followed by an intraperitoneal inoculation of KM12-L4 human colon cancer cells. Seprafilm membrane was placed under the incision or on the right lateral abdominal wall; control groups received no Seprafilm membrane. In another group, Vicryl mesh was placed on the right lateral abdominal wall and removed after 1 minute to control for surgical trauma associated with biomaterial placement., Results: Intraperitoneal Seprafilm did not affect human colon cancer tumor metastasis, including the liver, spleen, and mesenteric lymph nodes. The application of a biomaterial such as Seprafilm or Vicryl mesh to the peritoneal sidewall away from the midline wound was associated with an increased rate of local tumor growth. This was likely because of the local trauma of biomaterial placement in the nude mouse model and not because of the presence of a foreign material., Conclusions: Our study suggests that Seprafilm does not affect tumor metastasis. Additionally, placement of biomaterials may cause local trauma that stimulates the formation of localized sidewall tumors in the nude mouse model. Further studies in other animal models and ultimately, in humans are required to unambiguously understand the safety of Seprafilm and other biomaterials in cancer patients.