Background: Perfusion index (PI) could reflect peripheral flow. Preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA) will have left-to-right shunt across PDA causing less blood flow to the lower legs. Objective: To evaluate pre- and postductal PI differences (ΔPI) in hsPDA. Methods: Preterm infants with gestational age <34 weeks were assessed for ΔPI on days 1, 3, and 7 of life with simultaneous echocardiography. Based on echocardiography, each infant was categorized into hsPDA, non-hsPDA, and no PDA. Results: Thirty infants (16 males), median age 31 weeks (interquartile range, IQR, 29-32) and weight 1,490 g (IQR 1,100-1,670) were enrolled. On days 1 and 3 of life, the ΔPI of infants with hsPDA (1.57%, IQR 0.28-2.32, n = 14, and 1.32%, IQR 0.28-1.83, n = 10) were significantly higher than those without hsPDA (0.14%, IQR -0.03 to 0.30, n = 16, and 0.08%, IQR -0.07 to 0.26, n = 20), p = 0.009 and 0.005, respectively. At all time points (days 1, 3, and 7 of life, n = 84), ΔPI >1.05% had sensitivity, specificity, positive predictive value, and negative predictive value of 66.7, 100, 100, and 86.4%, respectively, to detect hsPDA. Conclusion: The pre- and postductal PI differences were significantly related to the hemodynamic changes of PDA and might be useful to detect hemodynamically significant PDA.