In a prospective controlled trial hemostatic effectiveness of a novel collagen-based composite (CoStasis) was compared with a collagen sponge applied with manual pressure at diffusely bleeding sites after surgical tumor resection. The proportion of subjects achieving complete cessation of bleeding within 10 minutes (i.e., hemostatic success) and the time to "complete hemostasis" were determined at raw surgical sites after tumor resection among 23 experimental and 30 control subjects. There was a similar distribution in tumor types (e.g., benign vs malignant) evaluated between treatment groups. A significantly greater proportion of experimental subjects achieved complete hemostasis within 10 minutes of observation compared with controls [23 of 23 (100%) vs 21 of 30 (70%); P = 0.003]. The median time required to achieve complete hemostasis was more than three times longer for subjects treated with the collagen sponge compared with subjects treated with CoStasis (243 vs 78 seconds; P = 0.0001). Approximately 80 per cent of experimental subjects achieved complete hemostasis within 2 minutes compared with only 35 per cent of controls. There were no adverse events related to the experimental treatment in this study. These results support the use of this novel hemostatic agent to control diffuse surgical site bleeding after tumor resection at diverse anatomical locations.