Background Earlier studies assessing mortality in polytrauma patients have focused on improving trauma care and reducing complications during hospital stay. The same studies have shown that the complication rate in these patients is high, often resulting in death. The aim of this study was to assess the incidence and causes of mortality in polytrauma patients in our institute. Secondarily, we assessed the donation and autopsy rates and outcome in these patients. Patients and methods All polytrauma patients (injury severity score≥16) transported to and treated in our institute during a period of 6 years were retrospectively analyzed. We included all patients who died during hospital stay. Prehospital and in-hospital data were collected on patients' condition, diagnostics, and treatment. The chance of survival was calculated according to the TRISS methodology. Patients were categorized according to the complications during treatment and causes of death. Logistic regression analysis was used to design a prediction model for mortality in major trauma. A statistical analysis was carried out. Results Of the 1073 polytrauma patients who were treated in our institute during the study period, 205 (19.1%) died during hospital stay. The median age of the deceased patients was 58.8 years and 125 patients were men. Their mean injury severity score was 30.4. The most common mechanism of injury involved fall from height, followed by bicycle accidents. Almost 50% of the patients underwent an emergency intervention. Almost 92% of the total population died because of the effects of the accident (primary trauma). Of these, 24% died during primary assessment in the emergency department. Most patients died because of the effects of severe head injury (63.4%), followed by exsanguination (17.6%). The most common type of complications causing death during treatment was respiratory failure (6.3%), followed by multiple organ failure (1.5%). Autopsy was performed in 10.4%. Organ donation procedure was performed in 14.5%. Permission for donation was not provided in almost 20% of the population. Conclusion The mortality rate in polytrauma patients in our institute is considerable and comparable with the international literature. Most patients die because of the effects of the accident (primary trauma). Autopsy and organ donation rates are low in our institution and leave room for substantial improvements in the future.