Background: Cardiac injury caused by a sharp object is a medical and surgical therapeutic challenge. Mortality risk factors have been identified but there are major discrepancies in the literature. The aim of this study was to analyse the management of victims of penetrating cardiac injuries before and after admission to hospital and the anatomical characteristics of these injuries in order to facilitate diagnosis of the most critical patients. Methods: To carry out this study, we conducted a retrospective analytical study with epidemiological data on victims of penetrating cardiac injuries. We included two types of patients, with those who underwent autopsy in our institution after death from sharp injury to the heart or great vessels and those who survived with treatment in the emergency department or intensive care unit between January 2015 and February 2022. Results: We included 30 autopsied patients and 12 survivors aged between 18 and 73 years. Higher mortality was associated with prehospital or in-hospital cardiorespiratory arrest (OR = 4, CI [1.71–9.35]), preoperative mechanical ventilation (OR = 10, CI [1.53–65.41]), preoperative catecholamines (OR = 7, CI [1.12–6.29]), preoperative and perioperative adrenaline (OR = 13, CI [1.98–85.46] and [1.98–85.46]), penetrating cardiac injury (OR = 14, CI [2.10–93.22]), multiple cardiac injuries (OR = 1.5, CI [1.05–2.22]) and an Organ Injury Scaling of the American Association for the Surgery of Trauma (AAST-OIS) score of 5 (OR = 2.9, CI [1.04–8.54]; p = 0.0329) with an AUC-ROC curve value of 0.708 (CI [0.543–0.841]). Conclusions: This study identified risk mortality factors in penetrating cardiac injury patients. These findings can help improve the diagnosis and management of these patients. The AAST-OIS score may be a good tool to diagnose critical patients.