In the United States, there is a paucity of studies examining sharp force injuries (SFIs), defined as an injury inflicted by cutting or stabbing with a sharp instrument. Few studies exist that discriminate between the injury patterns of suicidal or homicidal deaths incurred by SFI. In this retrospective study, all deaths secondary to SFI were evaluated at the Bexar County Medical Examiner’s Office from January 1988 through May 2010. Exclusion criteria were deaths occurring more than 24 hours after injury and wounds obscured by healing or extensive medical intervention. The following data were analyzed: age of decedent, sex, wound location, number of wounds, type of SFI (stab vs incised), visceral organ or vascular injury, concomitant injuries, and manner of death. Defensive injuries in homicides and hesitation marks in suicides were also recorded. A total of 418 deaths met inclusion criteria: 349 homicides, 54 suicides, 12 accidents, and 2 where the manner of death could not be determined.The average age of homicide victims was 35 years, whereas that of suicide victims was 47 years. Gender was not significantly different between the homicide and suicide groups. Homicide victims incurred a greater number of wounds per case compared with suicides, 5.3 versus 4.1, respectively, and had a greater number of stab wounds, 3.3 per case compared with 0.7 per case, respectively. Incisional wounds were statistically greater in suicides, with an average number of 3.3 per case compared with 2.1 in homicides.Injuries to the head, chest, and back were more common in homicides when compared with suicides, whereas injuries to the abdomen and extremities were more frequent in suicides. Comparison of major visceral and vascular damage between homicides and suicides revealed statistically greater injury to the heart, lungs, and thoracic vessels in homicides, but there was a greater frequency of injury to the vasculature of the extremities in suicides. The presence of additional (non-SFI) injuries was more common in homicides than in suicides. Hesitation marks/tentative wounds occurred in 35% of suicides, whereas defensive injuries occurred in 31% of homicides. This epidemiological study can assist the forensic pathologist in determining the most probable manner of death from SFI but does not substitute for a thorough examination of the circumstances of death and a meticulous autopsy.