Hemodynamically significant patent ductus arteriosus (hs-PDA) in very low birth weight (VLBW) infants continues to be an issue of research regarding the timing of treatment and which would be the most appropriate drug. Objective: To assess the outcome of prolonged treatment with paracetamol in the closure of hemodynamically significant patent ductus arteriosus in preterm newborns. Patients and Method: Retrospective study in VLBW infants with echocardiographic and clinical diagnosis of hs-PDA who received treatment with intravenous paracetamol at 15 mg/kg every 6 hours for 6 days. At the end of treatment, control echocardiography was performed. To evaluate possible side effects, biochemical tests were performed before and after treatment. Results: 62 VLBW infants with average weight and gestational age +/- SD of 1,094 +/- 257 g and 27,9 +/- 2,1 weeks, respectively, were evaluated. At the beginning of the treatment, the mean +/- SD ductal size was 2,2 +/- 0,5mm. The ductal closure rate with the first cycle of treatment was 69.4% (43/62) and with the second cycle, it increased to 87,1% (54/62). Surgical closure was required in 9,7% of the neonates (6/62). An increase in the incidence of retinopathy of prematurity and acute kidney injury was observed in preterm infants whose hs-PDA did not close with the first cycle of paracetamol. Biochemical tests after the treatment showed a significant decrease in creatinine and an increase in platelet count (p < 0,05). Conclusion: In VLBW infants with hs-PDA, prolonged treatment with intravenous paracetamol does not increase the ductal closure rate compared with the usual 3-day treatment.