BACKGROUND Globally, as in South Africa, obstetric hemorrhage (OH) remains a leading cause of maternal mortality and morbidity. Although blood transfusion is critical to OH management, the incidence and predictors of transfusion as well as their relation to human immunodeficiency virus (HIV) infection are poorly described. STUDY DESIGN AND METHODS A cross-sectional study was conducted of all peripartum patients at four major hospitals in South Africa (April to July 2012). Comprehensive clinical data were collected on patients who sustained OH and/or were transfused. Logistic regression was used to model risk factors for OH and transfusion. RESULTS A total of 15,725 peripartum women were evaluated, of whom 3969 (25.2%) were HIV positive. Overall, 387 (2.5%) women sustained OH and 438 (2.8%) received transfusions, including 213 (1.4%) women with both OH and transfusion. There was no significant difference in OH incidence between HIV-positive (2.8%) and HIV-negative (2.3%) patients (adjusted odds ratio [OR], 0.95; 95% confidence interval [CI], 0.72-1.25). In contrast, the incidence of blood transfusion was significantly higher in HIV-positive (3.7%) than in HIV-negative (2.4%) patients (adjusted OR, 1.52; 95% CI, 1.14-2.03). Other risk factors for transfusion included OH, low prenatal hemoglobin, the treating hospital, lack of prenatal care, and gestational age of not more than 34 weeks. CONCLUSION In the South African obstetric setting, the incidence of peripartum blood transfusion is significantly higher than in the United States and other high-income countries while OH incidence is similar. While OH and prenatal anemia are major predictors of transfusion, HIV infection is a common and independent contributing factor.