Background: The use of mineral (clay) or biologic (chitosan) materials has improved the efficacy of dressings used in the bleeding control of noncompressible areas. A series of novel manufactured products already evaluated in a vascular transection model was further compared in a severe vascular puncture injury model. Methods: Ten hemostatic dressings were tested in anesthetized Yorkshire swine hemorrhaged for 45 seconds in a femoral arterial puncture model. Application of these dressings was followed by 5 minutes of compression (about 175 mm Hg), and at 15 minutes, 500 mL resuscitation fluid (Hextand) was infused during a 30-minute period. The animals were monitored for a 3-hour experimental observation period. Primary outcomes were incidence of bleeding after dressing application and animal survival. Results: Blood loss was 18.8% ± 5.2% estimated blood volume (EBV) after 45 seconds of free bleeding. Relative performance of dressings is characterized as groups of dressings that performed similarly. Recurrence of bleeding after application was observed with most dressings and was lower with Woundstat, Celox, X-Sponge, and ACS+ (35% ± 49%) compared with FP-21, Hemcon, Chitoflex, and Bloodstop (79% ± 43%; P < .01). Blood loss after treatment was 25.3% ± 18.4% EBV for the top four dressings and 53.0% ± 18.4% EBV for the bottom four (P < .05). Survival was higher for top four vs bottom four dressings (78% ± 12% vs 25% ± 0%, respectively; P < .01). Overall performance of these dressings according to survival, incidence of bleeding, and post-treatment blood loss, yielded similar ranking as with a previously tested transection injury model. Conclusions: The findings indicated that the efficacy of Woundstat, Celox, X-Sponge, and ACS+ were similar and superior in improving survival, hemostasis, and maintenance of mean arterial pressure in an actively bleeding wound caused in this severe vascular injury model.