Preterm birth remains a global health concern and is one of the most common pregnancy complications associated with perinatal morbidity and mortality. Objective. This study investigated placental pathology and its associations with obstetric, maternal and neonatal outcomes in the Eastern Cape region of South Africa in order to help understand its associations with preterm birth in that region. Methods. In this prospective study, placentas were collected consecutively from patients attending a public tertiary referral hospital in South Africa, delivering preterm (n=100; 28-34 weeks gestational age) and term (n=20; >36 weeks gestational age). Placentas were submitted for histopathology, and comparisons with maternal characteristics and neonatal outcomes in preterm birth were undertaken. Results. Histological analysis revealed pathology in all preterm placentas (100%), with maternal vascular malperfusion (47%) and abruptio placentae (41%) most commonly identified. Acute chorioamnionitis (21%) was associated with term births (p=0.002). Maternal characteristics and neonatal outcomes significantly associated with preterm birth included preeclampsia (p=0.006), neonatal respiratory distress syndrome (p=0.004) and neonatal jaundice (p=0.003). Intrauterine demise (p=0.004), and alcohol abuse (p≤0.005) were significantly associated with term delivery. The number of mothers delivering preterm who were HIV positive was high (41%). Conclusion. The pathology identified in all preterm placentas supports the need to update institutional policies for submission of placentas from all preterm births for histopathology, particularly in countries with a high burden of preterm birth.