This prospective, controlled trial evaluated the hemostatic effectiveness of an experimental collagen-based composite (CoStasis), compared to a collagen sponge applied with manual pressure at diffusely-bleeding muscle-flap donor sites. Hemostatic success, time to "controlled bleeding," and time to "complete hemostasis" were determined at raw muscle-flap harvest sites among 22 experimental and 25 control subjects. There was a similar distribution in large-sized (e.g., latissimus dorsi) and moderate-sized (e.g., rectus abdominis) muscle flaps evaluated between treatment groups. More than twice the percentage of experimental subjects achieved complete hemostasis within 10 min of observation, compared to controls (100 percent vs. 48 percent, p < 0.0001). Time to controlled bleeding and complete hemostasis also favored the experimental group at statistically highly significant levels (p < 0.0001 for both comparisons). For example, greater than 60 percent of experimental subjects achieved complete hemostasis within 2 min compared to only 5 percent of controls. There were no adverse events related to the experimental treatment in this study. These results support the use of this investigational hemostatic agent to control diffuse bleeding at muscle-flap donor sites.