Background Hemorrhage is the leading cause of preventable battlefield death. Non-compressible injuries to junctional regionsaccount for 20 of these deaths and present a challenge to medical care providers. A novel minisponge-based dressing MSD, has been developed to control junctional hemorrhage. The MSD is a syringe applicator filled with compressed chitosan coated mini- sponges which are delivered directly into the wound cavity. Initial published results for MSD are promising but further evaluation ofsafety and efficacy is warranted. Methods In a swine model of uncontrolled junctional hemorrhage by subclavian artery SCA and veinSCV transection, animals were randomly assigned to three hemostatic dressing treatment groups n 10 per group MSD and standard-of-care hemostatic dressing with and without three minutes of manual compression SCHD and SCHD-NC, respectively. Blood loss was measured during a 30-second free bleed immediately following injury, dressing application, a 3-4 minute wait period and a 60 minute observation period. Primary endpoints were application time, blood loss, hemostasis, and survival. Statistical significance was determined by one-way ANOVA. Results Baseline values for weight, blood pressure, hematocrit, injury cavity volume and SCA and SCV diameters, were not different between groups. Blood loss during free-bleed, overall blood loss and hemostasis were also not different between groups. However, pack time and blood loss during application were lower p0.05 in the MSD group compared to the SCHD-WC and SCHD-NC groups. Conclusion No differences in survival, hemostasis or overall blood loss were observed betweenthe three groups, however, application time and blood loss during application were lower with MSD compared to the two SCHD groups.