We prospectively investigated whether the wound-protective Alexis (Applied Medical, Rancho Santa Margarita, CA) wound retractor was effective in preventing surgical site infection (SSI). We examined the actual condition of SSI in a 12-month randomized, controlled trial consisting of 221 patients who had undergone nontraumatic gastrointestinal surgery. The patients were divided into a With Alexis retractor group (n = 111) and a Without Alexis retractor group (n = 110). We also analyzed SSI separately on the basis of surgical sites such as gastric surgery or colorectal surgery. Overall estimation showed a significant decrease in wound infection (superficial incisional SSI) in the With Alexis retractor group. In the analysis based on surgical sites, a significant decrease in wound infection was noted in the With Alexis retractor group, the members of which had undergone colorectal surgery. There was no significant difference between the two groups in the occurrence of organ/space SSI, including anastomotic leak or intraperitoneal abscess. It was suggested that the use of the Alexis wound retractor would protect surgical wounds from contamination by bacteria and thus prevent infection.