Building on the work of Zimring, Vinson, and Sarvesvaren and Jayewardene, findings are presented on the weapon (or instrumentality) effect in homicidal violence. Data on weapons, wounds, and emergency medical response times were collected in St. Louis for 248 victims of severe assaults and homicides. Analysis confirms that firearms are more lethal than knives, and that large-caliber handguns are more lethal than small-caliber weapons. However, the data also show complex interactions among weapons and wounds, and suggest that many fatalities can be avoided, especially with knives, if medical authorities are notified quickly and if ambulance crews convey victims to experienced trauma centers within 20 minutes of dispatch.