Background Preterm birth complications are one of the leading causes of death among children under 5 years of age. Despite advances in medical care, many survivors face a lifetime of disability, including mental and physical retardation, and chronic lung disease. More recently, both allogenic and autogenic cord blood cells have been applied in the treatment of neonatal conditions such as hypoxic-ischemic encephalopathy (HIE) and bronchopulmonary dysplasia (BPD). Objective To assess the safety of autologous, volume- and red blood cell- (RBC-) reduced, noncryopreserved umbilical cord blood (UCB) cell infusion to preterm infants. Method This study was a phase I, open-label, single-arm, single-center trial to evaluate the safety of autologous, volume- and RBC-reduced, noncryopreserved UCB cell (5 × 107cells/kg) infusion for preterm infants <37 weeks gestational age. UCB cell characteristics, pre- and postinfusion vital signs, and laboratory investigations were recorded. Clinical data including mortality rates and preterm complications were recorded. Results After processing, (22.67 ± 4.05) ml UCB cells in volume, (2.67 ± 2.00) × 108 cells in number, with (22.67 ± 4.05) × 106 CD34+, (3.72 ± 3.25) × 105 colony forming cells (CFU-GM), and (99.7 ± 0.17%) vitality were infused to 15 preterm infants within 8 hours after birth. No adverse effects were noticed during treatment. All fifteen patients who received UCB infusion survived. The duration of hospitalization ranged from 4 to 65 (30 ± 23.6) days. Regarding preterm complications, no BPD, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP) was observed. There were 1/15 (7%) infant with intraventricular hemorrhage (IVH), 5/15 (33.3%) infants with ventilation-associated pneumonia, and 10/15 (66.67%) with anemia, respectively. Conclusions Collection, preparation, and infusion of fresh autologous UCB cells to preterm infants is feasible and safe. Adequately powered randomized controlled studies are needed.