Background: There is a paucity of data regarding the impact of retroperitoneal hematoma (RPH) volumes, as detected by computed tomography (CT) scanning, on patient morbidity and mortality. Therefore, we wanted to determine the natural history of RPHs and the effect of size on local and systemic outcomes. Methods: We performed a volumetric analysis of CT-documented RPHs managed at our institution between 1985 and 2006 along with a retrospective chart review. Results: We included 81 cases of RPH in this study. The mean Acute Physiology, Age, and Chronic Health Evaluation II (APACHE II) score was 12.8 ± 0.72 (score ± SE). By univariate analysis, the size of the hematoma showed a significant correlation with the development of local mass effects, delayed mass effects, 6-month mortality, major morbidity, pulmonary complications, fluid overload, and the requirement for operative evacuation (p < 0.05). Receiver operating characteristic analysis revealed that a size ≥1600 cm3 was >80% sensitive and specific for predicting a delayed mass effect or an increase in 6-month mortality. Multivariate analysis controlling for factors such as APACHE II and packed red blood cells transfused showed that the volume of the RPH was an independent predictor for the development of local mass effects, pulmonary insufficiency, and fluid overload. Conclusions: Large RPHs are clearly associated with worse patient outcomes. Surgical intervention may be warranted for the treatment of RPHs ≥1600 cm3.