Hypertension is an uncommon but significant problem in high-risk neonates and infants, and the spectrum of potential causes is broad. Here, we describe an extremely premature infant (birth weight, 728 g; gestational age, 27 weeks) with multiple complications and hypertension. During admission, umbilical artery catheters were used for a period of time, and he suffered from respiratory distress syndrome, intraventricular hemorrhage, pulmonary hemorrhage, patent ductus arteriosus, pericardial effusion, heart failure, repeated sepsis, anemia, thrombocytopenia, chronic lung disease, and progressive liver damage. He was treated with multiple medications, including erythropoietin, indomethacin, epinephrine, dopamine, aminophylline, multiple antibiotics, amphotericin B, and total parenteral nutrition. Hypertension was first noted when he was 41 days old, with spontaneous remission. It then recurred, reaching higher than 100 mmHg when he was almost 4 months old. After stopping erythropoietin, hypertension subsided for a short period of time and went up again. Multiple factor-related hypertension in this premature infant was considered. Related literature on hypertension in premature infants is reviewed. In conclusion, multiple factors can influence blood pressure and may induce hypertension in high-risk premature infants. Thus, blood pressure should be closely monitored in high-risk premature infants. Judicious use of all medications and interventions are crucial to decrease the incidence of hypertension in high-risk premature infants.